High fetal bisphenol A exposure enhances IL22 secretion: A proinflammatory cytokine.

BACKGROUND: Bisphenol A (BPA) is an industrial product, widely used in human consumed types of equipment that can be transmitted orally, by inhalation or through dermal absorption and is detectable in many body fluids including cord blood. A correlation between BPA concentration in maternal serum and cord blood has been demonstrated previously, suggesting a possible transfer of BPA via the transplacental path. OBJECTIVE: Our objective is to determine the impact of cord blood BPA level on cytokine responses. METHODS: In this cross-sectional study, healthy pregnant women who delivered healthy newborns followed by the Obstetrics and Gynecology Department between September 2016 to June 2017 were enrolled. Cord blood samples were obtained and BPA and IL4, IL5, IL10, IL17, IL22, IFN gama and TGF beta levels were studied by ELISA. RESULTS: Among 197 deliveries, 176 of them were included in the study. Due to lack of cut-off value, BPA levels were stratified as percentiles. No statistically significant difference was detected in comparison of cytokine levels based on BPA concentrations below and above the 25th and 50th percentiles. Significantly higher IL22 levels (p = 0.007) and increased ratio of IL22/TGFß (p = 0.04) were detected in those with BPA level above 75th percentile (>19.16 ng/ml) compared to the below group. CONCLUSIONS: This in vivo real-life study demonstrated that very high BPA levels in cord blood of expectant mothers enhances IL22 secretion in cord blood which is a proinflammatory cytokine. Studies evaluating long term immunological effects on those highly exposed newborns are necessitated.

Planning and approach to allergen-specific immunotherapy in polyallergic patients.

Allergy immunotherapy (AIT) is currently the only disease-modifying treatment for allergic-respiratory diseases. Polysensitization may increase the severity of current disease resulting in subsequent asthma development in patients with allergic rhinitis. Due to the absence of general recommendations for the practical approach to polysensitized patients, clinical management is not standardized. The correlation between sensitizations and clinical symptoms, elimination of possible pollen cross-reactivities and principles of homologous allergen groups will guide the allergists to deduce the most relevant allergens for AIT. In the highlight of the previously proposed approach strategies to polyallergic patients, hereby we propose a revised practical stepwise approach based on the current European Medicine Agency (EMA) guidelines. However, more supporting data from well-designed, controlled, future studies are needed to improve clinical management recommendations for AIT in polyallergic patients.

Headliner in Physiology and Management of Childhood Asthma: Hypothalamic-Pituitary-Adrenal Axis.

Asthma is the most common chronic inflammatory disease of children. Inhaled corticosteroids (ICS) are the cornerstone of asthma therapy which are the most effective, commonly used treatment of persistent asthma. Mostly, studies on the relationship between asthma and cortisol have focused on side effects of treatment. Recently, asthmatic patients not treated with ICS have been reported to have an attenuated activity and/or responsiveness of their Hypothalamic-Pituitary- Adrenal (HPA) axis. Moreover, it has been proposed that asthma worsening with stress may be due to a dysfunctional HPA axis, or cortisol insensitivity due to chronic psychological stress through impaired glucocorticoid receptor expression or function. Although long-term ICS treatment might produce adrenal suppression or iatrogenic Cushing syndrome, improvement of adrenal function has also been detected in some of asthmatic cases. Thus, the response scheme of HPA axis still contains undiscovered features in asthma. The management of asthma can be improved by increasing knowledge on the role of HPA axis in asthma pathophysiology. The risk for side effects of ICS can be minimized through increased awareness, early recognition of at-risk patients and regular patient follow-up. This review was written to draw attention to the role of HPA axis in both asthma and its treatment and to illustrate a follow up algorithm of HPA axis in the management of asthma.

Evaluation of Dose Dependent Maternal Exposure to Bisphenol A on Thyroid Functions in Newborns.

Bisphenol A (BPA) is an endocrine-disrupting chemical compound that is mainly used in industrial products as packaging and plastics. It usually transmits to humans via oral route from food-contact material. BPA has demonstrated to be found in body fluids with a higher amount of fetal tissues due to bio-accumulation. Although it has been reported to affect the endocrine system, results on thyroid functions of newborns are conflicting. The aim of the present study is to demonstrate the effect of different levels of BPA in cord blood on the thyroid functions of newborns, according to gender. METHODS: The study population included 88 newborns. The BPA levels, Thyroid stimulating hormone (TSH) and free thyroxine (fT4) levels of cord blood were measured. In addition, SPINA-GT (thyroid' incretory capasity), TSH Index (TSHI), standardized TSHI (sTSHI) were calculated and demographic characteristics of participants were noted. RESULTS: The mean of cord blood BPA was 4.934 ± 2.33 ng/mL. When evaluated according to quantiles of BPA, no association was found between BPA and thyroid hormone levels, as well as, SPINA-GT, TSHI, sTSHI in both genders. CONCLUSION: Although BPA has been shown to contaminate cord blood, no significant effect was detected on thyroid hormones, SPINA-GT, TSHI and sTSHI. Further investigations with larger study populations are warranted.

A milestone in house dust-mite-allergen immunotherapy: the new sublingual tablet S-524101 (actair).

Subcutaneous allergen-specific immunotherapy has long been used in the treatment of allergic rhinitis and/or asthma and its efficacy has been confirmed. However, due to the discomfort of injections and the risk of severe adverse reactions, alternative routes of allergen administration have emerged. Delivery of allergens through the mucosal route had been proposed and investigated thoroughly, confirming the sublingual route to be the most efficacious. Later, the efficacy and safety of this route have been documented by numerous controlled trials both for house dust mite (HDM) and pollens. Recently, sublingual orodispersable grass pollen allergen tablets were in use followed by the newly developed HDM allergen tablets with satisfactory clinical results: Moreover, very recently 1 year of HDM tablet treatment was demonstrated to exert its clinical efficacy 1 year after discontinuation of tablet IT. The persistence of efficacy after only 1 year of treatment is a new and promising era. Currently, Sublingual Immunotherapy is the most easily administered and safe treatment option until more immunogenic, less allergenic and more efficient allergen extracts are developed.

Risk factors for persistence of asthma in children: 10-year follow-up.

OBJECTIVE: Risk factors related to the outcome of childhood asthma are not yet well established. We aimed to investigate the long-term outcome for children with asthma to determine the risk factors in predicting persistence of disease. METHODS: Sixty-two children with asthma were evaluated retrospectively at the end of a 10-year follow-up. Patients were asked to complete a questionnaire requesting clinical information, and underwent physical examination, skin prick testing, a pulmonary function test and bronchial provocation testing. Immunologic parameters evaluated were allergen-specific IgE and IgG4 levels, and allergen-induced generation of CD4(+)CD25(+) cells. RESULTS: Mean age at final assessment was 15.9 ± 3.6 years, and duration of follow-up was 10.30 ± 1.27 years. Fifty percent of patients outgrew their asthma during the 10-year follow-up period. All the non-atopic patients outgrew their disease during the study period, whereas 67% of atopic patients did not. We identified two risk factors independently related to the persistence of symptoms: presence of bronchial hyper-responsiveness and presence of rhinitis. Atopic children who were in remission demonstrated significantly higher allergen-induced CD4(+)CD25(+) T cells compared to healthy controls. CONCLUSIONS: Atopy, presence of rhinitis, positive and presence of bronchial hyper-reactivity are important risk factors for the persistence of asthma in children. Allergen-induced CD4(+)CD25(+) T cells were higher in the atopic children who outgrew their disease, implicating an immunological mechanism of asthma remission in children.

Comparing subcutaneous and sublingual immunotherapy: what do we know?

PURPOSE OF REVIEW: Although allergen-specific sublingual (SLIT) and subcutaneous immunotherapy (SCIT) have been demonstrated to be clinically effective with similar immunological responses, head-to-head studies comparing those two modes of allergen administration in terms of onset of clinical improvement along with simultaneous immunological responses and underlying mechanisms of preventive effect are scarce. The present review will update current data on this issue. RECENT FINDINGS: Compared with SLIT, SCIT provides a rapid onset of clinical improvement by eliciting a simultaneous surge in production of T helper 1 (Th1) and T regulatory cell (Treg) cytokines and blocking antibodies. Similar immunological and clinical responses are evoked quite later, with no effect on Immunoglobulin G (IgG)4 levels during SLIT. Increases in TGFß secretion due to nonrelevant allergens during SLIT may explain the preventive effect on new sensitizations. SUMMARY: SLIT and SCIT are both clinically effective in the treatment of respiratory allergic diseases with slight differences in the early phase in terms of onset of clinical efficacy and simultaneous immunological responses. Both SLIT and SCIT induce similar T-cell responses in time, but specific IgG4-blocking antibody responses are more prevalent following SCIT. Further head-to-head studies addressing the preventive effect of monotherapy and the efficacy and immunological responses of nonrelated multiallergen immunotherapy in polysensitized patients are warranted.

Does inhaled corticosteroid treatment result in a secondary immune deficiency predisposing to recurrent infections?

It is well known that long-term treatment with systemic steroids exerts immune-suppressive effects on the cellular immune system and increase the susceptibility to all types of intracellular infections. Inhaled corticosteroids have been the mainstay treatment for asthma for a long period and are generally accepted as safe with no or minimal systemic absorption. Although, these medications are usually used for long periods and sometimes in high doses, there is scarce evidence on their impact on cell mediated immunity, reactivation of tuberculosis in tuberculin skin test positive patients, innate and anti-viral immunity. Hereby, the studies on immune-suppressive effects of inhaled steroids are discussed focusing on cell mediated and antiviral immunity.

Is calprotectin a marker of tobacco smoke related inflammation?: a pilot study in children.

CONTEXT: Environmental tobacco smoke (ETS) related inflammation has an anorexigenic effect through affecting the release of appetite-modulating mediators, leptin and ghrelin. Elevated serum calprotectin levels are found in a variety of inflammatory conditions. OBJECTIVE: To study the relation between ETS and body mass index (BMI), as well as serum levels of leptin, ghrelin and calprotectin. MATERIALS AND METHODS: A cross-sectional study was performed by searching the smoking status of parents. After filling in the questionnaires, parents were phoned and children were invited to supply fasting blood samples in order to measure serum levels of leptin, ghrelin and calprotectin, and to calculate their BMIs. Participant children were divided into Group 1 (n = 51), those who are not exposed to and Group 2 (n = 46), exposed to indoor ETS. RESULTS: There were no statistical difference in BMI, leptin and ghrelin levels between Group 1 and Group 2 (p values are 0.85, 0.87 and 0.42, respectively), but serum calprotectin levels were statistically higher in Group 2 (p = 0.003). DISCUSSION AND CONCLUSION: In this study serum levels of calprotectin were found to be higher in children with indoor ETS exposure where no relation was detected with BMI and serum levels of leptin and ghrelin. Increased serum levels of calprotectin might be an indicator of inflammation related to ETS exposure.

Osteoporosis: an ignored complication of CVID.

BACKGROUND: Multiple factors in common variable immunodeficiency (CVID) might interfere with optimal growth and maturation and potentially compromise bone health. METHODS: We aimed to evaluate bone mineral density (BMD) of patients with CVID using dual energy X-ray absorptiometry (DEXA) and investigate risk factors associated with decreased bone density. RESULTS: Twenty-two patients were included (M: 16, F: 6) with a mean age of 15.6 ± 9.0 yr. DEXA revealed osteopenia in 6/22 (27.3%) and osteoporosis in 9/22 (40.9%) at lumbar spine and osteopenia in 7/19 (37%) and osteoporosis in 3/19 (16%) at femoral neck sites. The age of subjects with osteoporosis was significantly higher than those without (21.6 ± 8.0 vs. 9.0 ± 5.7 yr; p < 0.0001). BMD z-scores were significantly lower in patients with bronchiectasis compared with those without (p = 0.03). Patients with osteoporosis at femoral neck site had lower forced expiratory volume in 1 s (FEV(1) ) (p = 0.024), FEV(1) /forced vital capacity (FVC) (p < 0.0001), PEF (p = 0.008), and FEF 25-75 (p = 0.013) values compared with the patients with normal BMD z-scores. Low serum 25(OH) vitamin D levels were detected in 13/22 patients and low dietary calcium intake in 17/22 patients. BMD z-scores at femoral neck were lower in patients with low B-cell percentage (p = 0.03). BMD z-score at lumbar spine was correlated with folate (r = +0.63, p = 0.004) and serum immunoglobulin G levels (r = +0.430, p = 0.04). CONCLUSION: Osteoporosis appeared as an emerging health problem of patients with CVID, the risk increasing with older age and poorer lung function. Nutritional, biochemical, and immunologic factors appeared to take part in decreased BMD. Insight into the mechanisms of osteoporosis in CVID is crucial to develop preventive strategies.

A novel approach in allergen-specific immunotherapy: combination of sublingual and subcutaneous routes.

BACKGROUND: Subcutaneous allergen-specific immunotherapy (SIT) has an early onset of action, whereas repeated injections and safety concerns have limited its use in the pediatric age group. Meanwhile, the improved safety profile of the sublingual route has been accepted as an alternative despite its relatively late onset of action. OBJECTIVE: We sought to improve the efficacy and safety of SIT with a combination of the subcutaneous route in the build-up phase and sublingual maintenance in comparison with the sublingual or subcutaneous routes alone. METHODS: Fifty-one house dust mite-sensitized children with mild-to-moderate asthma were randomized into one of 4 groups to receive either (1) subcutaneous immunotherapy (SCIT), (2) sublingual immunotherapy (SLIT), (3) SCIT plus SLIT, or (4) pharmacotherapy. Clinical parameters were evaluated at baseline and months 1, 4, 12, and 18. Allergen-specific immunoglobulin levels and allergen-induced IL-5, IL-10, IL-13, IL-17, TGF-ß, and IFN-γ levels were evaluated as well. RESULTS: In the SCIT and SCIT plus SLIT groups, the number of asthma attacks and inhaled corticosteroid dosage decreased compared with baseline values at the months 4, 12, and 18 but only at month 12 in the SLIT group. The improvement in visual analog scores for rhinitis was significant only in the SCIT plus SLIT group. Increases in the levels of regulatory and T(H)1 cytokines were observed both in the SCIT and SLIT groups, with some differences in dynamics. Antigen-specific IgG(4) levels increased in the SCIT and SCIT plus SLIT groups but not in the SLIT group. Clinical symptom scores were correlated positively with IL-5 levels and negatively with antigen-specific IgG(4), IFN-γ, and TGF-ß levels. CONCLUSION: Our novel regimen of immunotherapy, SCIT plus SLIT, appeared promising in that it successfully combined the advantages of the 2 alternatives: rapid onset and potency in SCIT and safety and avoidance of injections in SLIT.

Serum immunoglobulin levels as a predictive factor for a better outcome of non-atopic childhood asthma.

Childhood asthma is a heterogeneous condition with different phenotypes. Hereby, we aimed to study impact of serum immunoglobulin levels on clinical phenotypes and outcome of asthma. Seventy-eight children (M: 26, F: 52) aged less than 10 yrs (mean = 8.56 ± 3.23 yrs) and diagnosed as mild-moderate persistent asthma, followed up for at least 1 yr were included into the study. Asthmatic children were divided into two groups based on serum immunoglobulin levels at admission and were evaluated with respect to demographic data, allergic sensitization, symptom scores, medication usage, pulmonary functions, and non-specific bronchial hyper-reactivity. The age at onset of symptoms (40.88 ± 32.02 vs. 23.04 ± 26.97 months) was significantly younger in children with hypogammaglobulinemia (n = 28) compared to normogammaglobulinemia group (n = 50) (p = 0.016). Mean follow-up duration was 3.8 ± 2.1 yrs. Atopic sensitization rate was higher in those with normal immunoglobulin levels (81.2% vs. 17.9%), (p < 0.0001). Normal serum immunoglobulin levels were associated with atopic asthma (OR, 4.5; 95% confidence interval (CI): 2.0-10.1). For the prediction of atopic asthma, having normal immunoglobulin levels yielded predictive values of: sensitivity = 88.6%, specificity = 71.8%, positive predictive value = 81.1%, negative predictive value = 82.1%. Furthermore, percentages of atopic dermatitis and allergic conjunctivitis, elevated serum total IgE levels, eosinophilia, and bronchial hyper-reactivity were more common in normogammaglobulinemia with asthma group (p = 0.040, p = 0.003, p = 0.024, p = 0.030, p = 0.040, respectively). Although marked reductions in asthma scores and inhaled corticosteroid usage were observed in both groups over time, the rate of decline was significantly higher and earlier in hypogammaglobulinemia group (p = 0.0001, p = 0.004, respectively). In conclusion, asthmatic children with hypogammaglobulinemia presented at an earlier age, with lower rates of atopy, and earlier clinical improvement accompanied with earlier discontinuation of inhaled corticosteroids than children with normal immunoglobulin levels. Our data demonstrated that in children currently named as early-onset non-atopic asthma, hypogammaglobulinemia might be accompanying, providing evidence for a different phenotype of childhood asthma.

Neonatal BCG vaccination induces IL-10 production by CD4+ CD25+ T cells.

To determine the optimal time of Bacillus Calmette-Guerin (BCG) vaccination for induction of Th1 immunity, we measured the interferon (IFN)-γ and interleukin (IL)-10 secretion in purified protein derivative (PPD)-stimulated peripheral blood mononuclear cell (PBMC) cultures in newborns vaccinated at birth or 2nd month of life. Moreover, role of CD4(+) CD25(+) T cells was studied by depletion assay at 8th month. Nineteen term and healthy newborns were randomized into two groups: Group I composed of 10 newborns vaccinated with BCG at birth and the remaining 9 (group II) at 2nd month of life. PBMCs were isolated at birth, 2nd and 8th months of age, and PPD-stimulated IL-10, 5 and IFN-γ secretion were assessed. The same measurements were repeated for IL-10 and IFN-γ after the depletion of CD4(+) CD25(+) T cells at the 8th month. Children vaccinated at birth demonstrated higher PPD-stimulated IFN-γ and IL-10 levels at 2 months of age when compared to non-vaccinated ones (p = 0.038 and p = 0.022, respectively), whereas at 8 months, no significant differences were detected between the two groups. Moreover, CD4(+) CD25(+)-depleted T-cell cultures resulted in lower PPD-stimulated IL-10 levels in those vaccinated at birth when compared to non-depleted condition at the 8th month (p < 0.001). BCG at birth upregulated PPD-stimulated IFN-γ secretion at the 2nd month and remained still detectable at 8 month after the vaccination, whereas those vaccinated at the 2nd month of life lacked that increase in IFN-γ response at the same time-point. Furthermore, depletion assays suggest that CD4(+) CD25(+) T cells are involved in PPD-stimulated IL-10 secretion in response to BCG vaccination.

Defects along the T(H)17 differentiation pathway underlie genetically distinct forms of the hyper IgE syndrome.

BACKGROUND: The hyper IgE syndrome (HIES) is characterized by abscesses, eczema, recurrent infections, skeletal and connective tissue abnormalities, elevated serum IgE, and diminished inflammatory responses. It exists as autosomal-dominant and autosomal-recessive forms that manifest common and distinguishing clinical features. A majority of those with autosomal-dominant HIES have heterozygous mutations in signal transducer and activator of transcription (STAT)-3 and impaired T(H)17 differentiation. OBJECTIVE: To elucidate mechanisms underlying different forms of HIES. METHODS: A cohort of 25 Turkish children diagnosed with HIES were examined for STAT3 mutations by DNA sequencing. Activation of STAT3 by IL-6 and IL-21 and STAT1 by IFN-alpha was assessed by intracellular staining with anti-phospho (p)STAT3 and -pSTAT1 antibodies. T(H)17 and T(H)1 cell differentiation was assessed by measuring the production of IL-17 and IFN-gamma, respectively. RESULTS: Six subjects had STAT3 mutations affecting the DNA binding, Src homology 2, and transactivation domains, including 3 novel ones. Mutation-positive but not mutation-negative subjects with HIES exhibited reduced phosphorylation of STAT3 in response to cytokine stimulation, whereas pSTAT1 activation was unaffected. Both patient groups exhibited impaired T(H)17 responses, but whereas STAT3 mutations abrogated early steps in T(H)17 differentiation, the defects in patients with HIES with normal STAT3 affected more distal steps. CONCLUSION: In this cohort of Turkish children with HIES, a majority had normal STAT3, implicating other targets in disease pathogenesis. Impaired T(H)17 responses were evident irrespective of the STAT3 mutation status, indicating that different genetic forms of HIES share a common functional outcome.

No association between tuberculin skin test and atopy in a bacillus Calmette-Guérin vaccinated birth cohort.

Previously, an inverse association was suggested between mycobacterial infection and atopy. We aimed to determine the association between tuberculin skin test (TST) and allergic manifestations in a birth cohort where all infants were vaccinated with bacillus Calmette-Guérin (BCG) at birth. Newborns were enrolled randomly and prospectively followed up for a period of 5 yr. Information on family history and environmental factors was obtained at birth, International Study of Asthma and Allergies in Childhood asthma questionnaire, physical examination, skin prick test to common inhalant and food allergens and TST were performed at 2 and 5 yr of age. Positive TST reactivity was defined as an induration of > or = 10 mm. A total of 399 newborns were enrolled, 293 and 125 were available for a followup visit at 2 and 5 yr of age respectively. The prevalence of ever asthma, rhinitis and allergen sensitization tended to increase while eczema decreased with time. No significant association was found between TST reactivity and ever and current wheeze, doctor diagnosed asthma or atopic sensitization both at 2 and 5 yr of age. This prospectively designed birth cohort study did not confirm the previously suggested inverse correlation between TST reactivity and atopic sensitization or any allergic manifestations in Turkish children vaccinated with BCG at birth.

Non-atopic asthma in children is related to maternal bronchial hyperreactivity.

Data on the pathogenic mechanisms underlying the development of non-atopic asthma in children are scarce. Our aim was to evaluate the association and compare the atopic status, pulmonary functions, bronchial hyperresponsiveness and serum total immunoglobulin E (IgE) levels of parents of atopic and non-atopic asthmatic children by using objective methods. Fifty-one asthmatic children aged 4-16 yr and their parents were included into the study. Initially the American Thoracic Society's Respiratory Disease questionnaire inquiring data on symptoms of asthma, rhinitis and past medical history was filled in. Afterwards, skin prick test with aeroallergens, pulmonary function and methacholine bronchial provocation tests and serum sampling for total IgE level determinations were carried out. Bronchial hyperresponsiveness to methacholine was significantly more common in the mothers of non-atopic children compared to those of atopic ones, although no significant difference was observed in the skin prick test reactivity, pulmonary function test parameters and serum IgE levels. Questionnaire data revealed that the presence of asthmatic symptoms such as wheezing and phlegm and doctor-diagnosed asthma were more common in the mothers of non-atopic children. Meanwhile, asthmatic symptoms were also found to be significantly more common in fathers of non-atopic children. Logistic regression analyses revealed that maternal PC(20) was the only predictive factor for the risk of displaying non-allergic asthma in children. The results demonstrate that among the risk factors studied, maternal bronchial hyperreactivity was associated with the development of asthma in non-atopic children.

Transfer of T cells from intranasal ovalbumin-immunized mice ameliorates allergic response in ova-sensitized recipient mice.

Mucosal immunotherapy is suggested as a treatment strategy for tolerance induction in allergic diseases. The purpose of this study was to determine the effect of transferred splenic T cells from intranasal ovalbumin (OVA)-immunized mice to naive mice before sensitization on its impact of cytokine production and airway histopathology. BALB/c mice in group I received intranasal immunotherapy (days1-6), carboxylfluorescein succinyl ester (CFSE)-labeled splenocytes or splenic T cells were i.v. transferred to naive recipients (group II) before OVA sensitization. Acute murine asthma model was established by two i.p. OVA injections (days 21 and 28) and seven OVA nebulizations (days 42-48) in groups I, II and III. Groups III and IV served as asthma model and control, respectively. CFSE-labeled cells in splenocytes and lymph node lymphocytes, lung histopathology, IL-4, IL-10, and interferon (IFN) gamma cytokines of recipients were analyzed 24 hours after OVA nebulization challenge. CFSE-labeled T cells from group I were detected in spleen and regional lymph nodes of the OVA-sensitized recipients (group II). Smooth muscle and thickness of airways were less in intranasal OVA immunotherapy and OVA-sensitized recipients when compared with the asthma model (p < 0.05). Area of inflammation was significantly suppressed in OVA-sensitized recipients compared with the asthma model (p < 0.01). IL-10 and IFN-gamma levels in splenocyte supernatants were significantly increased in intranasal immunotherapy and OVA-sensitized recipients compared with asthma model and controls (p < 0.01). IL-4 levels were significantly less in intranasal immunotherapy group and the OVA-sensitized recipient group when compared with asthma the model group (p < 0.05). This study suggests that intranasal immunotherapy with allergens regulates T-cell responses and ameliorates airway histopathology in sensitized mice, hence, encouraging mucosal tolerance induction as a suitable treatment of allergic diseases.

Treatment with Mycobacterium vaccae ameliorates airway histopathology in a murine model of asthma.

The objective of this study was to evaluate the effect of intratracheal (i.t.) or subcutaneous (s.c.) Mycobacterium vaccae treatment on lung histopathology and cytokine responses in a murine model of asthma. BALB/c mice were divided into four groups. To establish an asthma model, Groups I, II and III received intraperitoneal (i.p.) ovalbumin (OVA) and were challenged with i.t. OVA three times (days 41-47). On the same days, mice in Groups I and II were treated with i.t. and s.c. Mycobacterium vaccae, respectively. Mice in Group IV served as controls. On day 49, lungs were taken out for histopathological evaluation. Cytokine levels were determined in splenocyte culture supernatants by ELISA. The thickness of basement membrane and hyperplasic goblet cells in small airways were found to be significantly more in Group III than Group I. Furthermore, smooth muscle and epithelial thickness in small and large airways and hyperplasic goblet cell numbers in all sized airways of this treatment group were not significantly different from controls. Epithelial thickness in medium and large airways, hyperplasic goblet cells in all sized airways, and basement membrane in small and large airways were not significantly different in Group II when compared to controls. OVA-stimulated IL-5 levels was significantly higher in Group I when compared to Group III. OVA-stimulated IL-5 and spontaneous IL-5 levels were significantly higher in Group II than Group III. We demonstrate that subcutaneous and intratracheal Mycobacterium vaccae administered along with allergen has an ameliorating effect in the modulation of airway histopathological changes in OVA sensitized mice.

Mycobacterium vaccae immunization to OVA sensitized pregnant BALB/c mice suppressed placental and postnatal IL-5 and inducing IFN-gamma secretion.

Although the development of atopy in the newborn is determined by a multitude of factors, an intense Th1 stimulus early in life could be protective by facilitating a switch away from Th2. Aimed to determine the effect of single Mycobacterium vaccae (M. vaccae) immunization to OVA-sensitized pregnant mice on IL-5 and IFN-gamma secretion from placental lymphocytes and splenocytes of offspring. Pregnant BALB/c mice were divided into 4 groups, OVA-sensitized + M. vaccae immunized, OVA-sensitized, M. vaccae immunized and controls. Sensitization with OVA was initiated before mating, and aerosol OVA challenge were performed during pregnancy. M. vaccae immunization was performed on the 12(th) day of pregnancy. IL-5 and IFN-gamma levels of placental lymphocytes were analyzed on the 18(th) day of pregnancy and splenocytes of offspring on the 2(nd) and 28(th) days during postnatal period. A single administration of M. vaccae to OVA-sensitized pregnant mice downregulated IL-5 secretion and induced IFN-gamma secretion from placental lymphocytes. On the other hand, after M. vaccae immunization downregulation of IL-5 levels and upregulation of IFN-gamma secretion persisted in offspring when determined on 2(nd) and 28(th) days of life. Vaccination with M. Vaccae to OVA-sensitized pregnant BALB/c mice prevented Th2 immune responses by enhancing secretion of IFN-gamma and lowering IL-5 levels during pregnancy and the effect persisted during the postnatal period in offspring.