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1.
Int Immunopharmacol ; 75: 105809, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31425975

ABSTRACT

The psychostimulant drug modafinil has been used for many years for the treatment of sleep disorders. Recent studies have indicated that modafinil has immunomodulatory properties in the central nervous system (CNS) and peripheral immune cells. Thus, our aim was to determine the effects of in vivo therapeutic treatment with modafinil on the severity of clinical symptoms and immune response during the acute phase of experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis. Modafinil treatment, given after the onset of symptoms, resulted in an improvement of EAE symptoms and motor impairment, which was correlated with reduced cellular infiltrate and a decreased percentage of T helper (Th) 1 cells in the CNS. The spinal cord analysis revealed that modafinil treatment decreased interferon (IFN)-γ and interleukin (IL)-6 protein levels and down regulated genes related to Th1 immunity, such as IFN-γ and TBX21, without affecting Th17-related genes. Our research indicates that therapeutic modafinil treatment has anti-inflammatory properties in an EAE model by inhibiting brain Th1 response, and may be useful as adjuvant treatment for multiple sclerosis.


Subject(s)
Central Nervous System Stimulants/therapeutic use , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Immunologic Factors/therapeutic use , Modafinil/therapeutic use , Animals , Brain/drug effects , Brain/immunology , Cytokines/immunology , Encephalomyelitis, Autoimmune, Experimental/immunology , Female , Mice, Inbred C57BL , Spinal Cord/drug effects , Spinal Cord/immunology
2.
Vet Immunol Immunopathol ; 210: 28-37, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30947977

ABSTRACT

Information on the dynamics of the chicken immune system during bacterial or parasite challenge in the presence or absence of stressful situations may provide a better understanding of the complex mechanisms behind these diseases. Necrotic enteritis (NE) had been controlled previously by the proper use of antimicrobial agents; however, more recently, NE has reemerged in many countries. The imposed restrictions on antimicrobial use and/or the intensive productive programs implemented by producers are challenges the birds, leading to large host adaptive responses that in many instances are like those elicited by stressors. This study analyses the effects of heat stress on Th1/Th2 cytokine balance, pathological features, and Toll-like receptor expression in the small intestine of broiler chickens infected with Clostridium perfringens type A in the presence or absence of Eimeria spp. co-infection. This co-infection model was experimentally used because it reproduces the findings commonly observed in the field during avian NE. For this purpose, broiler chickens infected with C. perfringens and/or Eimeria spp. were reared in isolator chambers subjected or not to heat stress intermittently. It was observed that heat stress directs the expression of Th2-type cytokines, increases Toll-like receptor 4 expression in the intestine and reduces the disease severity induced by Eimeria spp. and C. perfringens infections alone or in combination, most likely as a consequence of stress-induced changes in brain-gut axis activity.


Subject(s)
Clostridium Infections/veterinary , Coccidiosis/veterinary , Coinfection/veterinary , Cytokines/immunology , Enterocolitis, Necrotizing/veterinary , Heat-Shock Response/immunology , Th1-Th2 Balance , Animals , Chickens , Clostridium Infections/immunology , Clostridium perfringens/immunology , Clostridium perfringens/pathogenicity , Coccidiosis/immunology , Coinfection/microbiology , Coinfection/parasitology , Corticosterone/blood , Disease Models, Animal , Eimeria/immunology , Enterocolitis, Necrotizing/immunology , Intestines/immunology , Intestines/microbiology , Intestines/parasitology , Neuroimmunomodulation
3.
Res Vet Sci ; 123: 273-280, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30711848

ABSTRACT

Heat stress has a relevant effect on animal health and productivity. Stress and environmental changes can contribute to disease development, such as avian necrotic enteritis (NE). The goal of this study was to analyze the effects of heat stress applied to broiler chickens in an experimental model of co-infection with Clostridium perfringens and Eimeria spp. Therefore, the current study was designed to analyze the effect of heat stress to broiler chickens in an experimental model of infection or co-infection with Clostridium perfringens and Eimeria spp. C. perfringens was given in the poultry feed and the Eimeria infection was induced by gavage with a live oocysts vaccine dose 30 times higher than the manufacturer recommendation. We observed a reduction in the secretory IgA concentration in the jejunum and ileum in heat-stressed chickens compared to non-stressed chickens. Decreased maximum scores of intestinal necrosis, crypt abscesses and transmural lesions were observed in the heat-stressed chickens co-infected and infected with Eimeria compared to the respective unstressed groups. Heat stress caused an increase the intestinal lesion scores in chickens infected with C. perfringens only. The crypt depth was greater in chickens from the heat-stressed groups compared to the non-stressed groups. We also demonstrated that HS decreased infection and/or Eimeria development in the intestinal epithelium, reducing the harmful potential of C. perfringens.


Subject(s)
Chickens/immunology , Clostridium Infections/veterinary , Coccidiosis/veterinary , Heat-Shock Response , Hypothalamo-Hypophyseal System , Pituitary-Adrenal System , Animals , Chickens/microbiology , Chickens/parasitology , Clostridium Infections/complications , Clostridium Infections/immunology , Clostridium perfringens/physiology , Coccidiosis/complications , Coccidiosis/immunology , Coinfection/veterinary , Eimeria/immunology , Necrosis/veterinary , Poultry Diseases/immunology , Poultry Diseases/microbiology , Poultry Diseases/parasitology
4.
Vet Sci ; 6(1)2019 Jan 09.
Article in English | MEDLINE | ID: mdl-30634470

ABSTRACT

Heat stress has been related to the impairment of behavioral and immunological parameters in broiler chickens. However, the literature is not clear on the involvement of neuroimmune interactions in a heat stress situation associated with bacterial and parasitic infections. The present study evaluated the production of monoamines and their metabolites in brain regions (rostral pallium, hypothalamus, brain stem, and midbrain) in broiler chickens submitted to chronic heat stress and/or infection and co-infection with Eimeria spp. and Clostridium perfringens type A. The heat stress and avian necrotic enteritis (NE) modulated the neurochemical profile of monoamines in different areas of the central nervous system, in particular, those related to the activity of the hypothalamus-hypophysis-adrenal (HPA) axis that is responsible for sickness behavior. C. perfringens and/or Eimeria infection, heat stress increased 5-hydroxytryptamine (5-HT), 4,4 dihydroxyphenylacetic acid (DOPAC), and DOPAC/dopamine (DA) in the rostral pallium; 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), homovanillic acid (HVA), HVA/DA, DOPAC/DA, and 5-hydroxyindoleacetic acid (5-HIAA)/5-HT in the hypothalamus; MHPG, 5-HIAA/5-HT, DOPAC/DA, and HVA/DA in the midbrain; and MHPG, DOPAC, HVA, HVA/DA, DOPAC/DA, and 5-HIAA/5-HT in the brainstem. Heat stress decreased noradrenaline + norepinephrine (NOR + AD) in all brain regions analyzed; 5-HT in the hypothalamus, midbrain, and brainstem; and DA in the midbrain. The results also showed the existence and activity of the brain-gut axis in broiler chickens. The brain neurochemical profile and corticosterone production are consistent with those observed in chronic stressed mammals, in animals with sickness behavior, and an overloading of the HPA axis.

5.
Neuroimmunomodulation ; 25(1): 34-41, 2018.
Article in English | MEDLINE | ID: mdl-29874677

ABSTRACT

PURPOSE: We have previously shown that domperidone-induced short-term hyperprolactinemia reduces the lung's allergic inflammatory response in an ovalbumin antigenic challenge model. Since purinergic receptor P2X7R activity leads to proinflammatory cytokine release and is possibly related to the pathogenesis of allergic respiratory conditions, the present study was designed to investigate a possible involvement of purinergic and prolactin receptors in this phenomenon. METHODS: To induce hyperprolactinemia, domperidone was injected intraperitoneally in rats at a dose of 5.1 mg × kg-1 per day for 5 days. P2X7 expression was evaluated by lung immunohistochemistry while prolactin receptor expression in bronchoalveolar lavage leukocytes was analyzed through flow cytometry. RESULTS: Previous reports demonstrated that rats subjected to short-term hyperprolactinemia exhibited a decrease in leukocyte counts in bronchoalveolar lavage, especially granulocytes. Here, it is revealed that hyperprolactinemia promotes an increased expression of prolactin receptors in granulocytes. Also, increased expression of purinergic P2X7R observed in allergic animals was significantly reduced by hyperprolactinemia. CONCLUSIONS: Both purinergic and prolactin receptor expression changes occur during the anti-asthmatic effect of hyperprolactinemia.


Subject(s)
Asthma/metabolism , Hyperprolactinemia/metabolism , Lung/metabolism , Receptors, Purinergic P2X7/biosynthesis , Animals , Asthma/chemically induced , Asthma/immunology , Gene Expression , Hyperprolactinemia/immunology , Leukocyte Count/trends , Lung/immunology , Male , Ovalbumin/toxicity , Rats , Rats, Wistar , Receptors, Purinergic P2X7/genetics , Time Factors
6.
Int Immunopharmacol ; 56: 43-50, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29335159

ABSTRACT

The dopaminergic antagonist drug Domperidone has immunomodulatory effects. We investigated the effects of repeated Domperidone treatment in a model of Lypopolyssacharide (LPS)-induced acute lung inflammation. Adult C57BL/6J mice were treated with either Vehicle or Domperidone for 5days, and challenged intranasally with LPS in the following day. The behavior of mice was analyzed in the open field and elevated plus-maze test before and 24h after LPS challenge. The bronchoalveolar lavage fluid, blood and lung tissue were collected 24h and 48h after LPS challenge. Domperidone treatment increased LPS-induced tumor necrosis factor (TNF) and interleukin (IL)-6 production in the bronchoalveolar lavage fluid, without altering tissue damage and the number of immune cells in the lungs and circulation. Locomotor and anxiety-like behavior were unchanged after Domperidone and/or LPS treatment. Cytokine data indicate that Domperidone promotes a change in activity of other cell types, likely alveolar epithelial cells, without affecting immune cell migration in the present model. Due to the role of these cytokines in progression of inflammation, Domperidone treatment may exacerbate a subsequent inflammatory injury.


Subject(s)
Acute Lung Injury/immunology , Domperidone/administration & dosage , Dopamine Antagonists/administration & dosage , Respiratory Mucosa/physiology , Animals , Bronchoalveolar Lavage Fluid/immunology , Disease Progression , Domperidone/adverse effects , Dopamine Antagonists/adverse effects , Humans , Inflammation Mediators/metabolism , Interleukin-6/metabolism , Lipopolysaccharides/immunology , Male , Mice , Mice, Inbred C57BL , Respiratory Mucosa/drug effects , Tumor Necrosis Factor-alpha/metabolism
7.
Article in English | MEDLINE | ID: mdl-28499899

ABSTRACT

The wake-promoting drug Modafinil has been used for many years for treatment of Narcolepsy and Excessive Daytime Sleepiness, due to a dopamine-related psychostimulant action. Recent studies have indicated that Modafinil prevents neuroinflammation in animal models. Thus, the aim of the present study was to evaluate the effect of Modafinil pretreatment in the Lipopolysaccharide (LPS)-induced sickness and depressive-like behaviors. Adult male C57BL/6J mice were pretreated with Vehicle or Modafinil (90mg/Kg) and, 30min later, received a single saline or LPS (2mg/Kg) administration, and were submitted to the open field and elevated plus maze test 2h later. After 24h, mice were subjected to tail suspension test, followed by either flow cytometry with whole brain for CD11b+CD45+ cells or qPCR in brain areas for cytokine gene expression. Modafinil treatment prevented the LPS-induced motor impairment, anxiety-like and depressive-like behaviors, as well as the increase in brain CD11b+CD45high cells induced by LPS. Our results indicate that Modafinil pretreatment also decreased the IL-1ß gene upregulation caused by LPS in brain areas, which is possibly correlated with the preventive behavioral effects. The pharmacological blockage of the dopaminergic D1R by the drug SCH-23390 counteracted the effect of Modafinil on locomotion and anxiety-like behavior, but not on depressive-like behavior and brain immune cells. The dopaminergic D1 receptor signaling is essential to the Modafinil effects on LPS-induced alterations in locomotion and anxiety, but not on depression and brain macrophages. This evidence suggests that Modafinil treatment might be useful to prevent inflammation-related behavioral alterations, possibly due to a neuroimmune mechanism.


Subject(s)
Benzhydryl Compounds/pharmacology , Dopamine Agents/pharmacology , Illness Behavior/drug effects , Motor Activity/drug effects , Movement Disorders/drug therapy , Receptors, Dopamine D1/metabolism , Animals , Anxiety/drug therapy , Anxiety/metabolism , Anxiety/pathology , Benzazepines/pharmacology , Brain/drug effects , Brain/metabolism , Brain/pathology , Cell Movement/drug effects , Cell Movement/physiology , Depression/drug therapy , Depression/metabolism , Depression/pathology , Disease Models, Animal , Escherichia coli , Illness Behavior/physiology , Lipopolysaccharides , Macrophages/drug effects , Macrophages/metabolism , Macrophages/pathology , Male , Mice, Inbred C57BL , Modafinil , Motor Activity/physiology , Movement Disorders/etiology , Movement Disorders/metabolism , Movement Disorders/pathology , Neuroimmunomodulation/drug effects , Neuroimmunomodulation/physiology , Receptors, Dopamine D1/antagonists & inhibitors , Wakefulness-Promoting Agents/pharmacology
8.
Article in English | MEDLINE | ID: mdl-28919446

ABSTRACT

The wake-promoting drug Modafinil has been used for treatment of sleep disorders, such as Narcolepsy, excessive daytime sleepiness and sleep apnea, due to its stimulant action. Despite the known effect of Modafinil on brain neurochemistry, particularly on brain dopamine system, recent evidence support an immunomodulatory role for Modafinil treatment in neuroinflammatory models. Here, we aimed to study the effects of in vitro and in vivo Modafinil treatment on activation, proliferation, cell viability, and cytokine production by immune cells in splenocytes culture from mice. The results show that in vitro treatment with Modafinil increased Interferon (IFN)-γ, Interleukin (IL)-2 and IL-17 production and CD25 expression by T cells. In turn, in vivo Modafinil treatment enhanced splenocyte production of IFN-γ, IL-6 and tumor necrosis factor (TNF), and increased the number of IFN-γ producing cells. Next, we addressed the translational value of the observed effects by testing PBMCs from Narcolepsy type 1 patients that underwent Modafinil treatment. We reported increased number of IFN-γ producing cells in PBMCs from Narcolepsy type 1 patients following continuous Modafinil treatment, corroborating our animal data. Taken together, our results show, for the first time, a pro-inflammatory action of Modafinil, particularly on IFN-mediated immunity, in mice and in patients with Narcolepsy type 1. The study suggests a novel effect of this drug treatment, which should be taken into consideration when given concomitantly with an ongoing inflammatory or autoimmune process.


Subject(s)
Benzhydryl Compounds/pharmacology , Immunologic Factors/pharmacology , Interferons/metabolism , Wakefulness-Promoting Agents/pharmacology , Animals , Benzhydryl Compounds/therapeutic use , Cell Death/drug effects , Cell Death/physiology , Cell Proliferation/drug effects , Cell Proliferation/physiology , Cells, Cultured , Dose-Response Relationship, Drug , Humans , Immunologic Factors/therapeutic use , Male , Mice, Inbred C57BL , Modafinil , Narcolepsy/blood , Narcolepsy/drug therapy , Narcolepsy/immunology , Spleen/cytology , Spleen/drug effects , Spleen/immunology , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , Wakefulness-Promoting Agents/therapeutic use
9.
Physiol Behav ; 182: 128-136, 2017 Dec 01.
Article in English | MEDLINE | ID: mdl-29031549

ABSTRACT

Acute illness not only reduces the expression of social behavior by sick rodents, but can also lead to avoidance responses when detected by healthy, would-be social partners. When healthy animals interact with a sick partner, an intriguing question arises: does exposure to a sick conspecific elicit an anticipatory immune response that would facilitate defense against future infection? To address this question, healthy adult male Sprague-Dawley rats (N=64) were given a brief social interaction (30min) with a partner that was either sick (250µg/kg injection with lipopolysaccharide [LPS] 3h prior to test) or healthy (sterile saline injection). During this exposure, social behavior directed toward the healthy or sick conspecific was measured. Additionally, the impact of housing condition was assessed, with rats group- or isolate-housed. Immediately after social interaction, brains were harvested for cytokine assessments within socially-relevant brain structures (olfactory bulb, amygdala, hippocampus and PVN). As expected, behavioral results demonstrated that (i) there was a robust suppression of social interaction directed against sick conspecifics; and (ii) isolate-housing generally increased social behavior. Furthermore, examination of central cytokine expression in healthy experimental subjects revealed a modest increase in TNF-α in rats that interacted with a sick social partner, but only in the olfactory bulb. Among the LPS-injected partners, expected increases in IL-1ß, IL-6, and TNF-α expression were observed across all brain sites. Moreover, IL-1ß and IL-6 expression was exacerbated in LPS-injected partners that interacted with isolate-housed experimental subjects. Together, these data replicate and extend our prior work showing that healthy rats avoid sick conspecifics, and provide preliminary evidence for an anticipatory cytokine response when rats are exposed to a sick partner. These data also provide new evidence to suggest that recent housing history potently modulates cytokine responses evoked by LPS.


Subject(s)
Brain/metabolism , Cytokines/metabolism , Interpersonal Relations , Analysis of Variance , Animals , Brain/drug effects , Corticosterone/blood , Cytokines/genetics , Lipopolysaccharides/pharmacology , Male , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley
10.
Neuroimmunomodulation ; 24(1): 40-53, 2017.
Article in English | MEDLINE | ID: mdl-28787722

ABSTRACT

OBJECTIVES: Cohabitation with Ehrlich tumor-bearing (ETB) mice induced behavioral, neurochemical, hormonal, and immune effects in the conspecifics as a consequence of stress-induced activation of the sympathetic nervous system (SNS) with catecholamine release. In the current study, the nonspecific ß-AR blocker d,l-propranolol and the specific ß2-AR blocker ICI-118.551 were employed as pharmacological tools to assess the extent to which catecholamines participated in the effects induced by cohabitation with ETB mice. METHODS: Two experiments were performed, 1 with d,l-propranolol treatment and the other with ICI-118.551. One mouse in the experimental group was called the "companion of the sick partner" (CSP) since it was forced to live in the same cage with 2 (experiment 1) or 1 (experiment 2) cage mate that had been i.p. injected with 5 × 106 Ehrlich tumor cells. RESULTS: The d,l-propranolol treatment, but not the ICI-118.551 treatment, attenuated the effects of cohabitation with 2 ETB mice on both open-field behavior and the hypothalamic levels and turnover rate of norepinephrine. The 2 ß-AR blockers were unable to change the serum corticosterone levels and adrenal weights of the CSP mice; however, these drugs abrogated the effects of cohabitation on neutrophil oxidative burst and phagocytosis. Finally, an increase in the 5-HT turnover rate was observed in the olfactory bulb of CSP mice compared to their respective controls, an effect that was not modified by ß-AR blockade. CONCLUSION: These results confirm and strengthen our hypothesis that the SNS is involved in the effects induced by cohabitation with ETB mice and point towards ß2-AR participation in the immune effects analyzed.


Subject(s)
Adrenergic Agents/pharmacology , Carcinoma, Ehrlich Tumor/immunology , Carcinoma, Ehrlich Tumor/psychology , Interpersonal Relations , Adrenal Glands/drug effects , Animals , Carcinoma, Ehrlich Tumor/drug therapy , Carcinoma, Ehrlich Tumor/metabolism , Catecholamines/metabolism , Corticosterone/blood , Disease Models, Animal , Exploratory Behavior/drug effects , Female , Flow Cytometry , Illness Behavior/drug effects , Mice
11.
Physiol Behav ; 169: 82-89, 2017 02 01.
Article in English | MEDLINE | ID: mdl-27884589

ABSTRACT

Cohabitation with Ehrlich ascitic tumor-injected conspecifics induces behavioral, neurochemical, endocrine and immune changes indicative of stress and immune impairment in female mice. The present work analyzed the effects of similar cohabitation in Swiss and Balb/C male mice. At least 12 pairs of male mice were divided into a control group and an experimental group. On experimental day 1 (ED1), one animal within each experimental pair was inoculated with 5×106 Ehrlich tumor cells intraperitoneally (i.p.); the other animal was kept undisturbed and was referred to as the CSP (companion of a sick partner). One male mouse of each control pair was treated i.p. with 0.9% NaCl (1mL/kg); the other animal (the CHP, companion of a healthy partner) was kept undisturbed. Cohabitation with a sick partner for 11days did not induce any behavioral, hypothalamic noradrenergic, corticosterone or adrenal weight changes in the Swiss CSP male mice compared to those of the Swiss CHP group. However, impairments in neutrophil phagocytosis and oxidative burst as well as increased levels of catecholamines were observed in Swiss and Balb/C CSP mice relative to CHP male animals of the same strains on ED11 and ED14, respectively. Moreover, after a challenge with 5×106 Ehrlich tumor cells on ED11 of cohabitation, the number and concentration of tumor cells found in the ascitic fluid were higher in the Swiss CSP male mice than in the CHP mice. These data suggest that the immune changes observed in Swiss and Balb/C male CSP mice after cohabitation with a sick cagemate might, ultimately, depend on the changes induced by catecholamines, as previously reported for CSP female mice. However, contrary to that reported in Swiss CSP female mice, changes in behavioral and hypothalamic noradrenaline activity were not found in the Swiss CSP male mice analyzed in this work. This fact suggests that male and female CSP mice might use similar immune but different CNS strategies against the threats posed by the tumor-bearing animals.


Subject(s)
Carcinoma, Ehrlich Tumor/immunology , Carcinoma, Ehrlich Tumor/psychology , Social Behavior , Adrenal Glands/pathology , Animals , Catecholamines/blood , Corticosterone/blood , Exploratory Behavior/physiology , Flow Cytometry , Housing, Animal , Hypothalamus/metabolism , Male , Methoxyhydroxyphenylglycol/metabolism , Mice , Mice, Inbred BALB C , Neoplasm Transplantation , Neutrophils/pathology , Norepinephrine/metabolism , Time Factors
12.
Poult Sci ; 95(5): 1005-14, 2016 May.
Article in English | MEDLINE | ID: mdl-26957631

ABSTRACT

The gut-brain axis is known to modulate behavioral and immune responses in animals; evidence supporting this modulation in chickens, however, is elusive. Here, we analyzed the effects of heat stress and/orClostridium perfringens (CP) infection on behavior, intestinal morphology, brain activity, and corticosterone serum levels in chickens. Broilers were randomly divided into 5 equal groups: a naïve group (N), a thioglycolate group (T), a thioglycolate heat-stressed group (T/HS35), an infected group (I), and an infected/stressed (I/HS35) group. Broilers in the I and I/HS35 groups were experimentally infected withClostridium perfringensfrom the 15th to the 19th day of life. Heat stress (35±1°C) was constantly applied to the broilers in the stressed groups from the 14th to the 19th day of life. Our data showed that heat stress andC. perfringensinfection produced significant differential responses in the chickens' behavior and in c-fosexpression in the paraventricular nucleus of the hypothalamus (PVN), nucleus taenia of the amygdala (Tn), medial preoptic area (POM), andglobus pallidus (GP) of the chickens. Heat stress ameliorated some of the intestinal lesions and the neuroendocrine changes induced byC. perfringensin the birds. Our results suggest the existence of clear relationships between the degree of intestinal lesions, the chickens' behavioral outcomes, brain activity, and serum levels of corticosterone. Together, they reinforce the importance of neuroimmunomodulation and especially of brain-gut axis interactions.


Subject(s)
Brain/metabolism , Chickens , Enteritis/veterinary , Gastrointestinal Tract/metabolism , Heat Stress Disorders/veterinary , Poultry Diseases/etiology , Animals , Clostridium Infections/pathology , Clostridium Infections/veterinary , Clostridium perfringens , Corticosterone/blood , Enteritis/etiology , Genes, fos/physiology , Heat Stress Disorders/metabolism , Male , Poultry Diseases/pathology
13.
Vet Immunol Immunopathol ; 171: 38-46, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26964716

ABSTRACT

Avian necrotic enteritis (NE) induced by Clostridium perfringens is a disease that affects mainly the first weeks of poultry's life. The pathogenesis of NE is complex and involves the combination of several factors, such as co-infection with different species of coccidia, immunosuppression and stress. Stress is one of the main limiting factors in poultry production. Although several studies emphasized the effects of stress on immunity, few works analyzed these effects on immunoglobulins and on germinal centres (GCs), which are specialized microenvironments, responsible for generating immune cells with high affinity antibodies and memory B-lymphocytes. Thus, the effects of heat stress associated or not with thioglycolate broth culture medium intake and/or C. perfringens infection on corticosterone serum levels, spleen GCs development and immunoglobulin production in broilers were evaluated. Results showed that heat stress, thioglycolate and C. perfringens per se increased corticosterone serum levels, although this was not observed in heat stressed and thioglycolate and C. perfringens-treated chickens. The serum levels of IgA, IgM and IgY were differently affected by heat stress and/or infection/thioglycolate. Heat stress decreased the duodenal concentrations of sIgA, which was accompanied by a reduction in GCs number in the duodenal lamina propria; a trend to similar findings of sIgA concentrations was observed in the chickens' jejunum. Changes in spleen and Bursa of Fabricius relative weights as well as in spleen morphometry were also noted in heat stressed animals, infected or not. Together, these data suggest that heat stress change GCs formation in chickens infected or not, which that may lead to failures in vaccination protocols as well as in the poultries' host resistance to infectious diseases during periods of exposure to heat stress.


Subject(s)
Chickens/immunology , Clostridium Infections/veterinary , Clostridium perfringens , Enteritis/veterinary , Heat-Shock Response , Poultry Diseases/immunology , Spleen/pathology , Animals , Body Weight , Clostridium Infections/immunology , Clostridium Infections/pathology , Corticosterone/blood , Duodenum/immunology , Enteritis/immunology , Enteritis/pathology , Germinal Center/immunology , Germinal Center/pathology , Hot Temperature , Immunoglobulins/immunology , Male , Organ Size , Poultry Diseases/microbiology , Poultry Diseases/pathology
14.
Life Sci ; 151: 281-287, 2016 Apr 15.
Article in English | MEDLINE | ID: mdl-26979776

ABSTRACT

AIMS: To evaluate the influence of lactation on lung immune function during allergic inflammation. MAIN METHODS: Female rats, 60-90days old, were divided into three groups: no lung allergy virgins (N group), ovalbumin (OVA)-immunized and sensitized virgins (V group), and OVA-immunized and sensitized lactating females (L group). On gestation day (GD) 10, all animals in L group received a subcutaneous injection of 0.1mg·kg(-1) OVA plus aluminum hydroxide. On GD17, the L group received a subcutaneous booster injection of 10µg OVA plus 10mg aluminum hydroxide. After 7days, an inhalatory challenge with 1% OVA was given in 15min sessions for 3 consecutive days. Animals from the V group received the same treatment, meaning both tests and time intervals between OVA treatment and inhalatory challenge were the same as in the L group. Twenty-four hours after the last inhalation session, the animals were euthanized, and the following tests were performed: total and differential bronchoalveolar lavage (BAL) and femoral marrow lavage (FML) leukocyte counts, quantification of tumor necrosis factor α (TNF-α) and interferon γ (IFN-γ) levels in BAL fluid, and quantification of plasma corticosterone and catecholamine levels. KEY FINDINGS: The L group presented lower BAL total leukocyte counts and decreases in the number of eosinophils and macrophages compared with the V group. They also expressed higher BAL IFN-γ and lower plasma corticosterone levels. Plasma norepinephrine levels were higher in the L group than in the N and V groups. SIGNIFICANCE: Lactating female rats presented less intense allergic lung inflammation. Our findings suggest that lactation may protect females from asthmatic crises.


Subject(s)
Hypersensitivity/immunology , Inflammation/immunology , Lactation/immunology , Lung/immunology , Administration, Inhalation , Aluminum Hydroxide/pharmacology , Animals , Bone Marrow/immunology , Bronchoalveolar Lavage Fluid/immunology , Catecholamines/blood , Corticosterone/blood , Female , Interferon-gamma/metabolism , Lactation/blood , Leukocyte Count , Lung/metabolism , Ovalbumin/administration & dosage , Ovalbumin/immunology , Rats , Tumor Necrosis Factor-alpha/metabolism
15.
Psychoneuroendocrinology ; 65: 1-8, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26685709

ABSTRACT

Predominantly emotional stressors activate a wide range of brain areas, as revealed by the expression of immediate early genes, such as c-fos. Chlorella vulgaris (CV) is considered a biological response modifier, as demonstrated by its protective activities against infections, tumors and stress. We evaluated the effect of acute pretreatment with CV on the peripheral and central responses to forced swimming stress in adult male rats. Pretreatment with CV produced a significant reduction of stress-related hypothalamic-pituitary-adrenal activation, demonstrated by decreased corticotrophin releasing factor gene expression in the hypothalamic paraventricular nucleus (PVN) and lower ACTH response. Hyperglycemia induced by the stressor was similarly reduced. This attenuated neuroendocrine response to stress occurred in parallel with a diminished c-fos expression in most evaluated areas, including the PVN. The data presented in this study reinforce the usefulness of CV to diminish the impact of stressors, by reducing the HPA response. Although our results suggest a central effect of CV, further studies are necessary to understand the precise mechanisms underpinning this effect.


Subject(s)
Brain/physiology , Chlorella vulgaris , Hypothalamo-Hypophyseal System/drug effects , Pituitary-Adrenal System/physiology , Proto-Oncogene Proteins c-fos/biosynthesis , Stress, Physiological/physiology , Adrenocorticotropic Hormone/drug effects , Adrenocorticotropic Hormone/metabolism , Animals , Brain/metabolism , Corticosterone/metabolism , Corticotropin-Releasing Hormone/drug effects , Corticotropin-Releasing Hormone/metabolism , Genes, fos , Hypothalamo-Hypophyseal System/metabolism , Hypothalamus/metabolism , In Situ Hybridization , Male , Paraventricular Hypothalamic Nucleus/metabolism , Pituitary-Adrenal System/metabolism , Proto-Oncogene Proteins c-fos/genetics , Proto-Oncogene Proteins c-fos/metabolism , RNA, Messenger/metabolism , Random Allocation , Rats , Rats, Sprague-Dawley , Stress, Psychological/genetics , Stress, Psychological/metabolism , Swimming
16.
Life Sci ; 142: 66-75, 2015 Dec 01.
Article in English | MEDLINE | ID: mdl-26477293

ABSTRACT

AIMS: Prolactin is a major immunomodulator. The present study evaluated the effects of short-term hyperprolactinemia induced by domperidone before ovalbumin antigenic challenge on the lung's allergic inflammatory response. MAIN METHODS: To induce hyperprolactinemia, domperidone was injected in rats at a dose of 5.1mg·kg(-1) per day, i.p., for 5days from 10th to 14th day after OVA immunization. Total and differential leukocyte counts from bronchoalveolar lavage (BAL), femoral marrow lavage (FML), and blood were analyzed. The percentages of mucus and collagen production were evaluated. Levels of corticosterone and prolactin in serum, interleukin-4 (IL-4), IL-6, IL-10, tumor necrosis factor α (TNF-α) in lung explants supernatants were measured and interferon gamma (IFN-γ) in bronchiolar lavage cells suspensions (BAL) was measured. KEY FINDINGS: The rats that were subjected to short-term hyperprolactinemia exhibited a decrease in leukocyte counts in bronchoalveolar lavage, cellularity decrease in femoral marrow lavage fluid, a lower percentage of mucus, and an increase in lung IL-4, IL-6, IL-10, TNF-α and IFN-γ expression. SIGNIFICANCE: Hyperprolactinemia induced before antigenic challenge decreased allergic lung inflammation. These data suggest that prolactin may play a role in the pathophysiology of asthma. The present study demonstrates a prospective beneficial side effect of domperidone for asthmatic patients.


Subject(s)
Asthma/immunology , Hyperprolactinemia/immunology , Lung/immunology , Animals , Asthma/blood , Asthma/chemically induced , Asthma/pathology , Cytokines/blood , Cytokines/immunology , Gene Expression Regulation/drug effects , Hyperprolactinemia/blood , Hyperprolactinemia/chemically induced , Hyperprolactinemia/pathology , Inflammation/blood , Inflammation/chemically induced , Inflammation/immunology , Inflammation/pathology , Lung/metabolism , Lung/pathology , Male , Prolactin/toxicity , Rats , Rats, Wistar , Time Factors
17.
Poult Sci ; 94(10): 2375-81, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26362974

ABSTRACT

Multiple factors, such as environment, nutritional status, and disease, induce stress in animals during livestock production. It has been shown that poultry exposed to stressors for prolonged periods had decreases in their performance parameters, mortality and decreased host resistance to pathogenic agents. It seems that early age stress may have long-lasting impact and could possibly modify the expression of their genetic potential on growth performance and immunity. This study aimed to discuss the effects of early-age heat stress on the blood lymphocyte phenotypes (B and T lymphocytes) and plasma immunoglobulin levels (IgM and IgG) in chickens vaccinated against paramixovirus of the Newcastle (NC) disease (LaSota strain). For this purpose, 96 male chickens (Cobb) were divided into 4 groups: 1) control (C), 2) heat-stressed (HS), 3) control vaccinated (C/V), and 4) heat-stressed and Vaccinated (HS/V). The NC vaccine was administered twice on experimental day (ED) 7 and ED14, and the heat stress (38 ± 1°C) was applied from ED2 to ED6. The data showed that HS increased the corticosterone serum levels in the HS group compared with the control groups (C and C/V groups). At ED7, increased concentrations of IgM were observed in birds in the HS and HS/V groups compared with C and C/V animals; chickens from the HS/V group presented increased IgG levels compared with those in the birds of the C group. The heat stress shifted the immune cell profile from B-lymphocyte to a T-cytotoxic and T-helper lymphocyte profile, and this immune cell pattern persisted until the end of the study period. It was concluded that heat stress immunomodulated the immune function response of the chickens to the NC disease vaccine challenge.


Subject(s)
Chickens/physiology , Heat-Shock Response , Newcastle Disease/prevention & control , Vaccination/veterinary , Animals , B-Lymphocytes/cytology , Corticosterone/blood , Enzyme-Linked Immunosorbent Assay/veterinary , Immunoglobulin G/blood , Immunoglobulin M/blood , Immunophenotyping/veterinary , Male , Random Allocation , T-Lymphocytes/cytology
18.
Avian Pathol ; 44(6): 490-7, 2015.
Article in English | MEDLINE | ID: mdl-26397826

ABSTRACT

We analysed the effects of cold stress (19 ± 1°C, 6 h /day, from the first to the seventh day of life) applied to specific pathogen free (SPF) chickens. On experimental Day 1 (ED1), chicks were divided into four groups: C (not infected and kept under thermoneutral condition); CS (not infected and cold stressed); PC (Salmonella Heidelberg (SH) infected and kept under thermoneutral condition) and PCS (SH infected and cold stressed). High concentrations of corticosterone were found in the cold stressed birds on ED7 and ED21, with a greater increase in birds of the PCS group. Stress or non-stressed SH-infected birds had high levels of norepinephrine on ED21. On ED21, an increased percentage and number of SH were found in birds of the PCS group. On ED7, a decrease in macrophages presenting MHCII, CD8(+) and CD8(+) γδ cells was observed in the chickens of the CS group. Decrease was observed in CD3(+) cells in the birds of the PCS group and increase in macrophages presenting MHCII cells and of the CD4(+)/CD8(+) ratio in chickens of the CS group on ED21. There was a decrease in CD8(+) γδ cells in birds of the CS group on ED21 and in the CD3(+) and CD8(+)cell numbers in chickens of the PCS group on ED21. Our results suggest that cold stress applied to chickens in the first 7 days of life increases both the hypothalamus pituitary adrenal axis and the sympathetic nervous system activities, leading to long-term immune cell dysfunction, thus allowing increased SH invasion and persistence within the birds' body.


Subject(s)
Chickens/immunology , Poultry Diseases/immunology , Salmonella Infections, Animal/immunology , Salmonella/immunology , Animals , Bacterial Load , Catecholamines/blood , Chickens/microbiology , Cold Temperature , Corticosterone/blood , Immunity , Macrophages/immunology , Poultry Diseases/microbiology , Salmonella/isolation & purification , Salmonella Infections, Animal/microbiology , Specific Pathogen-Free Organisms , Stress, Physiological
19.
Brain Behav Immun ; 43: 159-71, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25108214

ABSTRACT

Multiple sclerosis (MS) is characterized by an autoimmune response against myelin antigens driven by autoreactive T cells. Several lines of evidence indicate that environmental factors, such as previous infection, can influence and trigger autoimmune responses. However, the importance of the gestational period, particularly under inflammatory conditions, on the modulation of MS and related neuroinflammation by the offspring is unknown. This study aimed to evaluate the impact of prenatal exposure to lipopolysaccharide (LPS) during late gestation on the neuroinflammatory response in primary mixed glial cultures and on the progression of experimental autoimmune encephalomyelitis (EAE, an animal model of MS) in the offspring. LPS (Escherichia coli 0127:B8, 120µg/kg) was administered intraperitoneally to pregnant C57BL/6J mice on gestational day 17, and the offspring were assigned to two experiments: (1) mixed glial cultures generated using the brain of neonates, stimulated in vitro with LPS, and (2) adult offspring immunized with MOG35-55. The EAE clinical symptoms were followed for 30days. Different sets of animals were sacrificed either during the onset (7days post-immunization [p.i.]), when spleen and lymph nodes were collected, or the peak of disease (20days p.i.), when CNS were collected for flow cytometry, cytokine production, and protein/mRNA-expression analysis. The primary CNS cultures from the LPS-treated group produced exaggerated amounts of IL-6, IL-1ß and nitrites after in vitro stimulus, while IL-10 production was lowered compared to the data of the control group. Prenatal exposure to LPS worsened EAE disease severity in adult offspring, and this worsening was linked to increased CNS-infiltrating macrophages, Th1 cells and Th17 cells at the peak of EAE severity; additionally, exacerbated gliosis was evidenced in microglia (MHC II) and astrocytes (GFAP protein level and immunoreactivity). The IL-2, IL-6 and IL-17 levels in the spleen and lymph nodes were increased in the offspring of the LPS-exposed dams. Our results indicate that maternal immune activation during late gestation predispose the offspring to increased neuroinflammation and potentiate the autoimmune response and clinical manifestation of EAE.


Subject(s)
Autoimmunity/immunology , Brain/immunology , Cytokines/metabolism , Encephalomyelitis, Autoimmune, Experimental/immunology , Inflammation/immunology , Animals , Astrocytes/immunology , Astrocytes/metabolism , Brain/metabolism , Encephalomyelitis, Autoimmune, Experimental/metabolism , Female , Inflammation/metabolism , Male , Mice , Microglia/immunology , Microglia/metabolism , Motor Activity/immunology , Pregnancy
20.
Neuroimmunomodulation ; 22(3): 121-9, 2015.
Article in English | MEDLINE | ID: mdl-24714518

ABSTRACT

BACKGROUND/AIMS: This study aimed to verify if odor cues released by Ehrlich tumor-bearing mice are aversive and stressful. METHODS: Female mice were divided into a control group and an experimental group. One animal of each experimental pair of mice was inoculated with 5 × 10(6) Ehrlich tumor cells intraperitoneally; the other animal was kept undisturbed and was referred to as a CSP (companion of sick partner). One mouse of each control pair was treated intraperitoneally with 0.9% NaCl (1 mg/kg); the other animal (CHP, companion of healthy partner) was kept undisturbed. RESULTS: It was shown that, in relation to CHP, CSP mice (1) spent less time within the companion zone in a T-maze place preference test, (2) had increased levels of social interaction, (3) had increased levels of plasmatic adrenaline and noradrenaline and (4) displayed no changes in serum corticosterone levels before and after an immobilization stress challenge. It was also shown that (5) cohabitation with 2 tumor-bearing mice was more effective in decreasing neutrophil oxidative burst than cohabitation with 1 sick partner and (6) the presence of a healthy conspecific within the cage of the tumor-injected/CSP pair abrogated the effects of cohabitation on neutrophil activity. These results show that odor cues released by Ehrlich tumor-injected mice are aversive and induce psychological stress. CONCLUSION: We postulate that the aversive response induced by the chemosignals released by Ehrlich tumor-injected animals activates the sympathetic nervous system and causes the neuroimmunal changes that occur in the mice cohabiting with the sick mice.


Subject(s)
Carcinoma, Ehrlich Tumor/psychology , Cues , Escape Reaction/physiology , Odorants , Stress, Psychological/physiopathology , Analysis of Variance , Animals , Carcinoma, Ehrlich Tumor/physiopathology , Catecholamines/metabolism , Corticosterone/blood , Disease Models, Animal , Female , Interpersonal Relations , Maze Learning/physiology , Mice , Neutrophils/pathology , Oxidative Stress/physiology , Phagocytosis , Radioimmunoassay , Time Factors
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