A non-hepatotropic parasite infection increases mortality in the acetaminophen-induced acute liver failure murine model: possible roles for IL-5 and IL-6

We evaluated the effects of a non-hepatotropic parasite infection (Taenia crassiceps) on the outcome of acetaminophen-induced acute liver failure in mice. Uninfected and T. crassiceps infected mice orally received either 300 mg/kg acetaminophen or water as vehicle (n = 5 per group). Survival analysis, hepatocyte necrosis, alanine aminotransferase (ALT) levels, CYP2E1 protein, interleukin (IL-) 5, and IL-6 were assessed for all groups. All infected mice died within 16 h after exposure to acetaminophen (Tc+APAP group), whereas only one-third of uninfected animals exposed to acetaminophen (APAP group) died. Uninfected (Control group) and infected (Tc group) mice that received the vehicle showed no liver damage. Tc+APAP mice exhibited massive liver necrosis characterised by marked balloning degeneration of hepatocytes and higher serum ALT compared to Control, Tc, and APAP animals. Liver tissue from Tc+APAP mice also displayed increased expression of CYP2E1 protein and higher mRNA and protein levels of IL-5 and IL-6 compared to the other groups. These findings suggest that non-hepatotropic parasite infections may increase mortality following acute liver failure by promoting hepatocyte necrosis via IL-5 and IL-6-dependent CYP2E1 overproduction. This study identifies new potential risk factors associated with severe acute liver failure in patients.

Toxocara canis and the allergic process

The protective effect of infectious agents against allergic reactions has been thoroughly investigated. Current studies have demonstrated the ability of some helminths to modulate the immune response of infected hosts. The objective of the present study was to investigate the relationship between Toxocara canis infection and the development of an allergic response in mice immunised with ovalbumin (OVA). We determined the total and differential blood and bronchoalveolar lavage fluid cells using BALB/c mice as a model. To this end, the levels of interleukin (IL)-4, IL-5 and IL-10 and anti-OVA-IgE were measured using an ELISA. The inflammatory process in the lungs was observed using histology slides stained with haematoxylin and eosin. The results showed an increase in the total number of leukocytes and eosinophils in the blood of infected and immunised animals at 18 days after infection. We observed a slight lymphocytic inflammatory infiltrate in the portal space in all infected mice. Anti-OVA-IgE levels were detected in smaller proportions in the plasma of immunised and infected mice compared with mice that were only infected. Therefore, we concluded that T. canis potentiates inflammation in the lungs in response to OVA, although anti-OVA-IgE levels suggest a potential reduction of the inflammatory process through this mechanism.

The Clinical Characteristics of Steroid Responsive Nephrotic Syndrome of Children according to the Serum Immunoglobulin E Levels and Cytokines

PURPOSE: The nephrotic syndrome (NS) is characterized by the favorable response to glucocorticoid therapy and the development of NS may be associated with dysfunctional immune systems. In order to investigate the serum immunoglobulin E (IgE) levels and cytokines activity in pediatric NS, the total of 32 steroid responsive NS patients and 5 healthy controls were enrolled in this study. MATERIALS AND METHODS: All patients were divided into two groups according to the initial serum IgE levels, such as normal and high IgE group, and their clinical characteristics were evaluated. In addition, serum levels of interleukin (IL)-4, IL-5, IL-10 and transforming growth factor (TGF)-beta were compared and correlated with serum albumin, proteinuria by means of disease severity, and cytokines. RESULTS: In the high IgE group, the higher comorbidity of allergic diseases and relapsing rate, the longer duration of steroid therapy before initial remission, and the higher serum IL-4 and IL-5 levels were found. In all patients, initially higher serum levels of IL-4 and IL-5 declined to normal levels after steroid therapy, whereas the serum IL-10 levels showed no significant difference between nephrotic phase (heavy proteinuria) and remission phase (no proteinuria) of NS. The serum TGF-beta levels of the nephrotic phase were significantly lower than those of remission phase or control group, and returned to normal control levels after steroid therapy. CONCLUSION: This study indicates that initial IgE level is associated with steroid responsiveness and disease severity, and cytokine activities may also be related to the pathogenesis of pediatric steroid responsive NS.

Scabies is a neglected health problem

The disease "scabies" is a neglected worldwide health problem that is caused by the mite Sarcoptes scabiei that burrows in the stratum corneum of the skin. Scabies persists despite the availability of topical insecticides because the disease is transmitted before it is diagnosed and treated and significant resistance to insecticides has developed. The aim of this study was to investigate immunobiochemial response of the host's inflammatory/immune response to scabies during infestation. The number of eosinophil, neutrophil and serum interleukin [IL]-5 were assessed in 27 patients with 25 healthy control subjects. In the present study significantly higher number of eosinophil [13.90 +/- 2.40%vs. 3.02 +/- 1.33%; p<0.001] and highly significant elevation in neutrophil [%] in the scahies group compared to the healthy controls [35, 9 +/- 4.2%vs. 21.4 +/- 2.6%, p<0.001]. As regards IL-S [there was a highly significant elevation in lnterleukin-5 in the scabics group compared to the healthy normal controls [47.0 +/- 18.31 ugh vs. 10 +/- 3.13 ug/l p<0.001].The results of this study suggest that there is a potent inflammatory immune response during the infestation of sarcopties scabiei. In conclusion, scabies is a dangerous disease affecting the immune system and should be treated once discovered to prevent the hazards of being epidemics

Interleukin [IL]-12, IL-5 and total IgE in hepatosplenic schistosomiasis with or without asthma

There are a number of similarities between protective immune responses against schistosomiasis and asthma. Both are associated with elevated concentrations of IgE and eosinophilia. Chronic schistosomiasis is liked to Th1 like response with involvement of pro-inflammatory cytokines in schistosomal hepatosplenic disease process resulting in low level of IL-S. Meanwhile, association with asthma could modulate the immune response with shift to Th2 side resulting in marked elevation of IL-5 and eosinophilia. This work evaluated the levels of serum IgE, IL-5 and IL-12 in Schistosoma mansoni-infected asthmatic patients. A total of 100 subjects selected from Al-Azhar University's Hospitals were divided into three groups GI: 50 patients with hepatosplenic schistosomiasis associated with asthma. GII: 25 patients with hepatosplenic schistosomiasis without apparent asthma. GIII: 25 patients with neither bilharzial liver cirrhosis nor asthma as control group. All patients were subjected to full history taking and clinical examination, pulmonary function tests, total serum IgE, bilharzial antibody titre, stool and urine examination for parasites, liver function tests and serum IL-5 and IL-12. The results showed very high level of the total serum IgE in GI and GII compared to GIII. There was high significant difference in peripheral blood eosinophil%. GI and GII gave highest levels, IL-5 was elevated in GI, but low GII, IL-12 was high in GII than GI

Non-cancerous thyroid lesions: immunologic and surgical evaluation

The present study was designed to determine T helper-l/T helper-2 [Th[1]/Th[2]] pattern in patients with Graves' disease [GD], benign multinodular goiter [MNG] and Hashimoto thyroiditis [HT] and evaluate the applicability of near-total thyroidectomy as a therapeutic strategy for surgical interference. The study included 75 patients [56 females and 19 males; with mean age of 43.8 +/- 8.2 years] with thyroid swelling and 15 healthy volunteers [control group]. Patients underwent clinical examination including direct laryngoscopy using fiberoptic endoscopy, laboratory investigations and ultrasonographic and [99m] Tc pertechnetate scintigraphy for establishment of diagnosis. Patients with HT received medical treatment and were followed-up, while patients with GD and MNG underwent near-total thyroidectomy. Preoperative blood samples were collected from patients and control subjects for ELISA estimation of serum levels of interleukin-2 [IL-2], IL-18, IL-4 and IL-5. Patients were observed for appearance of postoperative manifestations of recurrent laryngeal nerve [RLN] palsy and/or hypoparathyroidism. Mean operative time, duration of wound drainage and hospital stay were recorded. The study included 43 patients with GD [8 of them had thyroid orbitopathy], 17 patients had MNG and the remaining 15 patients had HT. All patients had smooth intraoperative course and no patient had permanent RLN palsy, but 4 [6.7%] patients had transient unilateral RLN palsies that recovered spontaneously after a mean duration of 24.5 +/- 11.6 days. Temporary hypocalcaemia occurred in 9 patients [15%] and permanent hypoparathyroidism resulted in one [1.7%]. All patients developed wound edema, 7 patients had wound seroma and 2 patients had wound infection. Mean serum levels of lL-2, IL-4 and IL-5 were significantly higher in patients compared to control levels irrespective of the type of thyroid lesion. Mean serum levels of IL-18 were significantly higher in patients with HT and MNG disease and non-significantly higher in patients with GD compared to control levels. Moreover, mean serum levels of IL-2 and IL-18 were significantly higher and mean serum levels of IL-4 and IL-5 were significantly lower in patients with HT and MNG disease compared to those with GD and in MNG patients compared to those with HT. The percentage of postoperative increase of serum IL-2 and IL-18 levels relative to the median control level were significantly higher in patients with HT than in patients with GD or MNG with a significantly higher percentage of increase in patients with MNG compared to those with GD. On the other hand, the percentages of increase of IL-4 and IL-5 were significantly higher in patients with GD compared to patients with HT or MNG with a significantly but non-significantly higher percentage of increase of IL-5 and IL-4, respectively, in patients with MNG compared to those with HT. It could be concluded that there was a disturbed pattern of Th[1]/Th[2] cytokines in patients with non-cancerous thyroid lesion in favor of humoral pattern of immune response in GD with predominance of Th[2] cytokines and a Th[1]-pattern of immune response characteristic of cellular immunity is dominant in HT. Also, near total thyroidectomy was found appropriate therapeutic modality with transient minimal complications for patients with MNG or GD

Intracellular IL-5 expression by peripheral blood CD4[+] and CD8[+] T-cells in atopic and non-atopic asthma

There is evidence of CD8[+] and CD4[+] peripheral blood T cell activation in childhood atopic asthma. However, the immunopathology of non-atopic asthma in children remains unclear. We sought to investigate the intracellular IL-5 expression by peripheral blood CD4[+] and CD8[+] T cells in atopic and non-atopic asthmatic children in relation to asthma grading and severity of exacerbation, as well as is possible correlation to various inflammatory markers of asthma. The study comprised 35 atopic and 35 non-atopic asthmatic children enrolled during activity and 30 clinically healthy children. They were subjected to flow cytometric assessment of intracellular IL-5 expression in CD4[+] and CD8[+] T cell subsets as well as absolute eosinophil count, serum total IgE, eosinophil cationic protein [ECP], and urinary Leukotriene E4 [LTE4] estimation. Asthmatic children compiled all together and the atopic group showed highly significant increase in absolute eosinophil count, IgE% from high normal for age, serum ECP, urinary LTE4 / creatinine ratio, intracellular CD4[+] IL5, and CD8[+] IL5 T cell numbers as compared to the control group. Similar results were observed between the non-atopic asthmatic children and the control group. When the atopic and non-atopic asthmatic children were compared, the former group showed significantly higher values of all study parameters except the urinary LTE4, urinary creatinine ratio, and CD8[+] IL5 frequency. CD4[+] IL5 T cell number correlated positively with the absolute eosinophil count, IgE% and serum eosinophil cationic protein among the 70 asthmatic patients. Stepwise multi-regression analysis revealed CD4[+] IL-5 frequency to be an inverse independent variable for asthma exacerbation. Likewise, IL-5 production, either CD4[+] or CD8[+] T cells was an inverse independent variable for grading of asthma severity. Both CD8[+] and CD4[+] T cells contribute to the IL-5 production in asthmatic children whether atopic or non-atopic during disease activity. CD4[+] T cell IL-5 frequency estimation could be a useful marker for asthma exacerbation severity and both CD4[+] and CD8[+] T cell IL-5 frequencies might serve as markers for asthma grading

HIV binding to resting CD4 lymphocytes induces production of certain cytokines

Objective: To test the cytokine production in HIV infection

Design and methods: Cytokine profiles in two separate studies of HIV patients and controls are presented: Peripheral blood mononuclear cells [PBMC] from patients and controls were tested for the production of [interleukin [IL]-4, IL-5, IL-10, interferon [IFN]-gamma, and TNF-alpha] cytokines by enzyme-linked immunosorbent assay [ELISA]. Both spontaneous and mitogen-induced cytokine production was measured

Results: The serum cytokine profile is altered in HIV patients compared to normal subjects. We examined if HIV binding to resting CD4 T-cells induced production of cytokines, intracellular IL-4, IL-10. TNF-alpha, and IFN-gamma expression 48 hrs after mock- or HIV-exposure of resting T- cells and T-cell. We found that HIV binding to resting T-cells upregulated expression of IFN-gamma and TNF-alpha by 24 hrs], and these remained elevated during 60 hrs of observation HIV binding had no appreciable effect on IL-4 expression and at 48 hrs little effect on IL- 10. EIA measurements of released cytokines in culture supernatants further showed that TNF-alpha and IFN-gamma were produced, but IL-4 was not. Furthermore, by EIA analysis, IL-2 was not induced [data not shown], but IL-5 and IL-10 were at 3 days. It seems likely, then, that HIV-signaled resting CD4 T-cells can provide <> activity

Conclusions: The study herein was performed to more fully characterize HIV-signaled, resting CD4 lymphocytes. We found that HIV signaling also induced production of IFN-gamma, IL-5, IL-10 and TNF-alpha, but not IL-2 or IL-4. These cells, however, did not go into cell cycle. Further, they could secondarily respond to normal proliferation stimuli from anti-CDS cross-linking or PHA and enter into cell cycle and produce a greater number of cytokines, and they did not display any significant activation-induced apoptosis. Thus, resting CD4 lymphocytes are partially activated by HIV binding, resulting in enhanced expression of certain activation markers and cytokines

Association between Interleukin-5 and Body Mass Index among Iraqi asthmatic patients

Asthma is an allergic hypersensitivity disease in which many mediators play a role in its pathogenecity. One of these etiological agents are the mediators such as lnterleukin-5 [IL-5]. The aim of this study is to demonstrate the association between IL-5 and obesity in asthma development. One hundred and four sera samples for asthma cases have been studied in comparison with 41 non-asthmatic bronchitis as patient controls beside 30 apparently healthy controls. Cytokine has been estimated using ELISA method in correlation with Body Mass Index [BMI]. This study revealed a significant correlation between IL-5 concentration and BMI [P<0.05], particularly among females. There is certain correlation between obesity and asthma accompanied by IL-5

Interleukin-5 production by peripheral blood monocytes from asthmatic patients: effect of alveolar macrophages

This study aimed to assess the role of ALM in the pathogenesis of bronchial asthma by studying the effect of ALM derived from bronchoalveolar lavage [BAL] on IL-5 production by peripheral blood monocytes PBMC [including T lymphocytes] in cocultures in patients with bronchial asthma as compared to that in non asthmatic individuals. Nineteen patients with bronchial asthma were enrolled in this study. Ten normal non-smoker subjects were considered as controls. Patients were subjected to broncoalveolar lavage [BAL]. The lavage fluid was cultured in 3 wells; one with peripheral blood monocytes [PBMC], another with PBMC with mitogen stimulation and the third with PBMC with BAL cells and stimulation. Cultures were incubated and the supernatants were assayed for IL-5 by EL1SA. The mean [SD] age for the asthmatic patients was 37.67[9.66] years with a mean [SD] body mass index of 28.3[6.12]. Male constituted 53% [11/19] of the studied asthmatic patients. The levels of 1L-5 in the supernatant of resting PBMN cultures were significantly higher in patients with asthma in all three states [basal state, after PHA stimulation, in cocultures with ALM [mean [SD] = 219.45[68.34] ng/ml, range [100-320 ng/ml], 484.85[115048.01], range [170-670 ng/ml], 1118 [336.59], range [530-1800 ng/ml], respectively. The respective levels in the nonatopic normal subjects was [mean [SD]: 21.20[8.97], 26.8[10.10], 29.30[7.87]]. The differences between the three states in the asthmatic patients were highly significant. The changes between the three states in the non-asthmatic patients were insignificant. IL5 production by PBMN is markedly increased in asthmatic patients versus non-asthmatic subjects, furthermore, IL-5 production was markedly amplified by co-culturing PBMN with autologous ALM derived from BAL in the asthmatics patients. This is in contrast to the finidings in non-asthmatic subjects where IL5 production was not augmented by autologous ALM. The fact that ALM from non-asthmatic subjects functioned poorly as APC may represent a local inhibitory protective mechanism in the airways

Estudio de los niveles de CD23 soluble, IgE y eosinofilia en la respuesta inflamatoria del asma bronquial / Study of the levels of soluble CD23, I and E and eosinophile in the inflammatory reply of bronchial asthma

El CD23, descripto como una glucoproteína de 45 kDa, está relacionado con la activación de los linfocitos B y la regulación de la síntesis de IgE. Se degrada en fragmentos solubles (CD23s). Es una multicitocina involucrada en patologías con predominio de linfocitos TH2, tales como las enfermedades alérgicas, leucemia B crónica o en injerto de médula ósea. El 70 por ciento de los asmáticos presenta niveles de IgE aumentados. El eosinófilo es la célula central de la inflamación asmática. Objetivo: se evaluó la corrrelación entre niveles de CD23s, IgE sérica, eosinofilia sanguínea y esputo en asmáticos atópicos y por aspirina, frente a un grupo control de individuos normales. Pacientes: se estudiaron 27 pacientes atópicos: 14m, 13f, 10 asmáticos por AAS: 4m, 6f. Un grupo control de 10 sujetos: 5m, 5f. Nadie recibió corticoides en los dos meses previos. Se determinaron IgE total por ELISA Kabi-Pharmacia, CD23s por ELISA, Binding Site, MK112. Recuentos de eosinófilos en esputo y sangre periférica. Resultados: IgE:asmáticos atópicos: 500Ï252kU/l. Asmáticos por AAS: 68Ï27 kU/l. Controles: 51Ï20 kU/l<0.0005. CD23s: asmáticos atópicos: 7.65Ï2.25 ng/ml. Asmáticos por AAS: 3.4Ï0,95 ng/ml. Controles: 3.73Ï1.08 ng/ml; p<0.0005. Eosinófilos en esputo: asmáticos atópicos: 25Ï13 por ciento. Asmáticos por AAS: 23Ï13 por ciento. NS. Eosinofilia sanguínea: asmáticos atópicos: 685Ï316/mm3. Asmáticos por AAS: 555Ï190/mm3 NS. Control: 255Ï90mm3; p<0.0005. Conclusiones: nuestro estudio demuestra un incremento de la IgE y CD23s en los asmáticos atópicos. Los sensibles a aspirina no presentaron cambios significativos respecto del grupo control. La eosinofilia positiva se encontró en ambos grupos de asmáticos. Esto sugiere diferentes mecanismos inflamatorios en asma bronquial, con una vía común representada por los eosinófilos