Disturbance to early brain development is implicated in several neuropsychiatric disorders including autism, schizophrenia, and mental retardation. Epidemiological studies have indicated that the risk of developing these disorders is enhanced by prenatal maternal infection, presumably as a result of neurodevelopmental defects triggered by cytokine-related inflammatory events. Here, we demonstrate that the effects of maternal immune challenge between middle and late gestation periods in mice are dissociable in terms of fetal brain cytokine responses to maternal inflammation and the pathological consequences in brain and behavior. Specifically, the relative expression of pro-and anti-inflammatory cytokines in the fetal brains in response to maternal immune challenge may be an important determinant among other developmental factors for the precise pathological profile emerging in later life. Thus, the middle and late gestation periods correspond to two windows with differing vulnerability to adult behavioral dysfunction, brain neuropathology in early adolescence, and of the acute cytokine responses in the fetal brain.
Maternal infections during pregnancy increase the risk for schizophrenia and related disorders of putative neurodevelopmental origin in the offspring. This association has been attributed to enhanced expression of pro-inflammatory cytokines in the fetal environment in response to maternal immunological stimulation. In contrast, the specific roles of anti-inflammatory cytokines are virtually unknown in this context. Here, we demonstrate that genetically enforced expression of the anti-inflammatory cytokine interleukin (IL)-10 by macrophages attenuates the long-term behavioral and pharmacological consequences of prenatal immune activation in a mouse model of prenatal viral-like infection by polyriboinosinic-polyribocytidilic acid (PolyI:C; 2 mg/kg, intravenously). In the absence of a discrete prenatal inflammatory stimulus, however, enhanced levels of IL-10 at the maternal-fetal interface by itself also precipitates specific behavioral abnormalities in the grown offspring. This highlights that in addition to the disruptive effects of excess pro-inflammatory molecules, a shift toward enhanced antiinflammatory signaling in prenatal life can similarly affect cognitive and behavioral development. Hence, shifts of the balance between pro-and anti-inflammatory cytokine classes may be a critical determinant of the final impact on neurodevelopment following early life infection or innate immune imbalances.
Objectiveto assess the levels and determinants of interleukin (IL)-1β, IL-6, tumour necrosis factor (TNF)-α and C-reactive protein (CRP) in a healthy Caucasian population.Methodspopulation sample of 2884 men and 3201 women aged 35 to 75. IL-1β, IL-6 and TNF-α were assessed by a multiplexed particle-based flow cytometric assay and CRP by an immunometric assay.ResultsSpearman rank correlations between duplicate cytokine measurements (N = 80) ranged between 0.89 and 0.96; intra-class correlation coefficients ranged between 0.94 and 0.97, indicating good reproducibility. Among the 6085 participants, 2289 (37.6%), 451 (7.4%) and 43 (0.7%) had IL-1β, IL-6 and TNF-α levels below detection limits, respectively. Median (interquartile range) for participants with detectable values were 1.17 (0.48–3.90) pg/ml for IL-1β; 1.47 (0.71–3.53) pg/ml for IL-6; 2.89 (1.82–4.53) pg/ml for TNF-α and 1.3 (0.6–2.7) ng/ml for CRP. On multivariate analysis, greater age was the only factor inversely associated with IL-1β levels. Male sex, increased BMI and smoking were associated with greater IL-6 levels, while no relationship was found for age and leisure-time PA. Male sex, greater age, increased BMI and current smoking were associated with greater TNF-α levels, while no relationship was found with leisure-time PA. CRP levels were positively related to age, BMI and smoking, and inversely to male sex and physical activity.ConclusionPopulation-based levels of several cytokines were established. Increased age and BMI, and to a lesser degree sex and smoking, significantly and differentially impact cytokine levels, while leisure-time physical activity has little effect.
Objective: To assess the associations between obesity markers (BMI, waist circumference and %body fat) and inflammatory markers (interleukin-1β (IL-1β); interleukin-6 (IL-6); tumor necrosis factor-α (TNF-α) and high-sensitivity C-reactive protein (hs-CRP)). Methods: Population sample of 2,884 men and 3,201 women aged 35–75 years. Associations were assessed using ridge regression adjusting for age, leisure-time physical activity, and smoking. Results: No differences were found in IL-1β levels between participants with increased obesity markers and healthy counterparts; multivariate regression showed %body fat to be negatively associated with IL-1β. Participants with high %body fat or abdominal obesity had higher IL-6 levels, but no independent association between IL-6 levels and obesity markers was found on multivariate regression. Participants with abdominal obesity had higher TNF-α levels, and positive associations were found between TNF-α levels and waist circumference in men and between TNF-α levels and BMI in women. Obese participants had higher hs-CRP levels, and these differences persisted after multivariate adjustment; similarly, positive associations were found between hs-CRP levels and all obesity markers studied. Conclusion: Obesity markers are differentially associated with cytokine levels. %Body fat is negatively associated with IL-1β; BMI (in women) and waist circumference (in men) are associated with TNF-α; all obesity markers are positively associated with hs-CRP.
Background: Macular or maculopapular skin reactions are frequent events in drug allergy as well as in viral infections. Clinically, the differentiation may be difficult in the absence of a clear relationship to drug intake or failure to detect virus–specific antibodies of the IgM class. Studies on drug–specific T cell lines and T cell clones isolated from drug–allergic patients have suggested that these cells may represent a significant source of IL–5. On the other hand, viral infections are frequently associated with elevated IFN–γ levels. Objective: Determination of serum–cytokine levels to differentiate between drug– and virally induced skin eruptions. Patients: 18 patients suffering from acute drug allergy and 19 patients with acute measles, rubella or parvovirus infection. Measurements: Cytokine–ELISA (IL–5, IL–4 and IFN–γ) of sera collected during acute drug allergy or during acute measles, rubella or parvovirus infection. Results: In 12/18 patients with drug allergy, IL–5 and/or IL–4 were elevated. A significant correlation (rSpearman = 0.84) between IL–5 serum levels and eosinophil counts in the blood was found. No correlation was detected between IL–4 and blood eosinophilia or between IL–4 and IL–5 levels. After remission, IL–5 and IL–4 decreased to undetectable levels. IFN–γ on the other hand was not measurable in patients with drug allergy while elevated IFN–γ serum levels were detected in 17/19 patients with measles, rubella or parvovirus infection; 2 patients with acute virus infection had elevated IL–5, and/or IL–4 and IFN–γ levels. Conclusion: These data underline the distinct pathogenesis of these morphologically similar exanthemas and suggest that the combined analysis of eosinophilia in the blood, IL–4 and IFN–γ might help in differentiating skin eruptions.
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