Interleukin-10 regulation in normal subjects and patients with asthma
ABSTRACT Interleukin-10 or cytokine synthesis inhibitory factor has important antiinflammatory activities in immune diseases. We speculated that diminished IL-10 production in asthma would permit the unopposed synthesis of proinflammatory cytokines, contributing to the development and severity of asthma. Our data demonstrate constitutive secretion of IL-10 into bronchoalveolar lavage (BAL) fluid of normal, nonasthmatic subjects (130 +/- 61 pg/ml; n = 8). Asthmatic patients' BAL fluid was characterized by diminished concentrations of IL-10 (9 +/- 18 pg/ml; n = 8; p < 0.01 compared with that of normal subjects). By using the RNA-based polymerase chain reaction, we demonstrated that diminished IL-10 occurred as a result of inhibition of transcription. IL-10 transcription, but not protein, was observed at the time of the late asthmatic response. We speculate that the subsequent appearance of IL-10 protein could contribute to the resolution of the late asthmatic response. Similar to what was observed in the BAL fluid, peripheral blood mononuclear cells of patients with asthma demonstrated decreased spontaneous (0.01 +/- 0.01 ng/ml-asthmatic and 0.09 +/- 0.04 ng/ml-normal; p < 0.05) and stimulated (0.60 +/- 0.22 ng/ml-asthmatic and 1.69 +/- 0.49 ng/ml-normal; p < 0.05) IL-10 production compared with normal subjects. In support of the hypothesis that IL-10 mitigates the development of inflammation, we demonstrated that the addition of a neutralizing anti-IL-10 antibody to resting peripheral blood mononuclear cell cultures of normal subjects stimulated the spontaneous production of interferon-gamma (10.4 +/- 4.3 to 152.4 +/- 23.6 ng/ml; p < 0.01). Finally, we reasoned that corticosteroids might exert at least part of their antiinflammatory activity through the induction of IL-10 secretion. However, methylprednisolone inhibited the lipopolysaccharide-stimulated production of IL-10 (2.34 +/- 0.49 ng/ml IL-10 with lipopolysaccharide alone to 1.11 +/- 0.38 ng/ml in the additional presence of 10(-6) mol/L methylprednisolone; p < 0.05).
SourceAvailable from: Luminita A Stanciu[Show abstract] [Hide abstract]
ABSTRACT: Activation through different signaling pathways results in two functionally different types of macrophages, the pro-inflammatory (M1) and the anti-inflammatory (M2). The polarization of macrophages toward the pro-inflammatory M1 phenotype is considered to be critical for efficient antiviral immune responses in the lung. Among the various cell types that are present in the asthmatic airways, macrophages have emerged as significant participants in disease pathogenesis, because of their activation during both the inflammatory and resolution phases, with an impact on disease progression. Polarized M1 and M2 macrophages are able to reversibly undergo functional redifferentiation into anti-inflammatory or pro-inflammatory macrophages, respectively, and therefore, macrophages mediate both processes. Recent studies have indicated a predominance of M2 macrophages in asthmatic airways. During a virus infection, it is likely that M2 macrophages would secrete higher amounts of the suppressor cytokine IL-10, and less innate IFNs. However, the interactions between IL-10 and innate IFNs during virus-induced exacerbations of asthma have not been well studied. The possible role of IL-10 as a therapy in allergic asthma has already been suggested, but the divergent roles of this suppressor molecule in the antiviral immune response raise concerns. This review attempts to shed light on macrophage IL-10-IFNs interactions and discusses the role of IL-10 in virus-induced asthma exacerbations. Whereas IL-10 is important in terminating pro-inflammatory and antiviral immune responses, the presence of this immune regulatory cytokine at the beginning of virus infection could impair the response to viruses and play a role in virus-induced asthma exacerbations. © 2014 The Authors. Reviews in Medical Virology published by John Wiley & Sons Ltd. © 2014 The Authors. Reviews in Medical Virology published by John Wiley & Sons Ltd.Reviews in Medical Virology 11/2014; 25(1). DOI:10.1002/rmv.1817 · 5.76 Impact Factor
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ABSTRACT: The role of antigen-specific T cells in the mechanism of food allergy or maintenance of tolerance toward an innocuous antigen, such as cow's milk, is not yet fully understood.Objective The cow's milk–specific T-cell response of donors with various allergic backgrounds was investigated.Methods Cow's milk–specific T-cell clones (TCCs) were generated from the blood of children with persistent cow's milk allergy (CMA) and the blood of cow's milk–tolerant allergic and nonallergic control subjects. The TCCs were characterized by their antigen-specific proliferation, cytokine production, and activation status.ResultsCow's milk–specific TCCs of children with persistent CMA were TH2 skewed, and the production of IL-4 and IL-13 was significantly correlated with the expression of the activation marker CD25. TCCs of the allergic control subjects were characterized by a high production of IL-10, which was positively correlated with the production of IL-4 and IFN-γ and with the expression of CD25. TCCs derived from nonallergic control subjects had an attenuated response toward cow's milk in that they did not produce high levels of cytokines nor did they express high levels of surface markers. As in the allergic control subjects, in the nonallergic control subjects IL-10 production was positively correlated with the expression of CD25.Conclusion The activation status of T cells derived from persistent donors with CMA was associated with the production of IL-4 and IL-13, whereas activated TCCs of cow's milk–tolerant control subjects were characterized by the production of IL-10 and, to a lesser extent, IFN-γ. These findings suggest that activated CD4+ T cells (characterized by a high CD25 expression) might contribute to the tolerogenic immune response toward an antigen, such as cow's milk, through the production of IL-10.Journal of Allergy and Clinical Immunology 05/2004; 113(5):932-939. DOI:10.1016/S0091-6749(03)02778-7 · 11.25 Impact Factor
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ABSTRACT: Knowledge of the effects of early environmental and congenital factors on the natural history of asthma may provide important clues to the pathogenesis of asthma.Objective We assessed associations between potential, early determinants and the incidence and remission of asthma throughout life, and tested whether the strength and direction of these associations varied in childhood, adolescence, and adulthood.Methods The data pertaining to the individual asthma history of 18,156 subjects, age 0 to 44 years, who attended the clinical stage of the European Community Respiratory Health Survey were analyzed retrospectively by life-event methods. Onset of asthma was defined as age at the first attack, and asthmatic patients were considered to be in remission if they had not been under treatment or had an attack of asthma in the past 24 months. Onset and remission were evaluated in 3 time windows: <10, 10 to 20, and ≥20 years of age. The associations of asthma with early determinants were estimated by hazard ratios (HRs).ResultsA family history of asthma or allergy was associated with a higher risk of developing asthma (HR, 1.89; 95% CI, 1.67-2.13) and a lower chance of remission (HR, 0.79; 95% CI, 0.64-0.99) throughout life. No matter what one's genetic predisposition was, early, acute respiratory infections were associated with an increased lifelong risk of asthma onset (pooled HR, 3.19; 95% CI, 2.75-3.69), whereas early contact with older children, which is a marker of prolonged, intermittent exposure to infectious agents, conferred permanent protection against asthma (HR, 0.84; 95% CI, 0.74-0.96) and increased the chance of remission in childhood asthma (HR, 1.50; 95% CI, 1.10-2.04). Pet ownership had a protective effect only in childhood (HR, 0.78; 95% CI, 0.74-0.96), whereas maternal smoking did not show a significant association with asthma. Female sex was negatively associated with the onset of asthma in childhood (HR, 0.62; 95% CI, 0.52-0.75) and positively in adulthood (HR, 2.01; 95% CI, 1.61-2.51). The pattern of associations was similar in sensitized (positive assay to specific IgE) and nonsensitized asthmatic patients.Conclusion Genetic predisposition and exposure to infectious agents are major early determinants that influence a subsequent history of asthma. The length and type of exposure to infectious agents seem able either to promote or to suppress an anti-inflammatory process, unrelated to IgE, which can partially interfere with an acquired predisposition for asthma.Journal of Allergy and Clinical Immunology 05/2004; 113(5):845-852. DOI:10.1016/S0091-6749(04)00997-2 · 11.25 Impact Factor