Cytokine expression in rhinovirus- vs. respiratory syncytial virus-induced first wheezing episode and its relation to clinical course

Rhinovirus (RV) and respiratory syncytial virus (RSV) are common causes of bronchiolitis. Unlike an RSV etiology, an RV etiology is associated with a markedly increased risk of asthma. We investigated the cytokine profiles of RV- and RSV-induced first wheezing episode and their correlation with prognosis. We recruited 52 sole RV- and 11 sole RSV-affected children with a severe first wheezing episode. Peripheral blood mononuclear cells (PBMCs) were isolated during acute illness and 2 weeks later and stimulated in vitro with anti-CD3/anti-CD28. Culture medium samples were analyzed for 56 different cytokines by multiplex ELISA. Recurrences were prospectively followed for 4 years. In adjusted analyses, the cytokine response from PBMCs in the RV group was characterized by decreased expression of interleukin 1 receptor antagonist (IL-1RA), interleukin 1 beta (IL-1 beta), and monocyte chemoattractant protein-1 (MCP-1) and increased expression of eosinophil chemotactic protein 2 (eotaxin-2), thymus- and activation-regulated chemokine (TARC), and epithelial-derived neutrophil-activating peptide 78 (ENA-78) in the acute phase and increased expression of fractalkine in the convalescent phase compared to those in the RSV group. An analysis of the change in cytokine expression between study points revealed an increased expression of fractalkine and IL-1 beta and decreased expression of I-309 (CCL1) and TARC in the RV group compared to those in the RSV group.. Considering hospitalization time, a significant non-adjusted group x cytokine interaction was observed in the levels of interferon gamma (IFN-gamma), macrophage-derived chemokine (MDC), IL-1RA, and vascular endothelial growth factor (VEGF), indicating that a higher expression of cytokine was associated with shorter hospitalization time in the RSV group but not in the RV group. A significant interaction was also found in interleukin 6 (IL-6), but the cytokine response was not associated with hospitalization time in the RSV or RV group. In the RV group, increased expression of I-309 (CCL1) and TARC was associated with fewer relapses within 2 months, and decreased expression of interleukin 13 (IL-13) and increased expression of I-309 (CCL1) were associated with less relapses within 12 months. Differences in cytokine response from PBMCs were observed between RV- and RSV-induced first severe wheezing episode. Our findings also reveal new biomarkers for short- and medium-term prognosis in first-time wheezing children infected with RV or RSV.Peer reviewe

Asthma, allergy and the Olympics

OBJECTIVE: There are no comprehensive surveys relating the reported high prevalence of asthma and allergic diseases in athletes to comorbidities and immune changes associated with intense chronic exercise. This 12-year survey aims to evaluate several clinical, functional and immunological parameters in order to assess features, trend and burden of asthma, allergy, infections and autoimmune diseases, in a large homogeneous population of Olympic athletes. METHODS: Six hundred and fifty-nine Italian Olympic athletes were studied through four cross-sectional surveys performed between 2000 and 2012 before the Summer and Winter Olympics. Clinical diagnosis of allergic, autoimmune and infectious diseases was complemented by: skin-prick tests (n = 569); pulmonary function tests (n = 415); total (n = 158) and specific (n = 72) serum IgE; serum autoantibodies (n = 30), cytokines and growth factors (n = 92); flow cytometry (n = 135). RESULTS: The prevalence of asthma and/or exercise-induced bronchoconstriction was 14.7%, with a significant increase (P = 0.04) from 2000 (11.3%) to 2008 (17.2%). The prevalence of rhinitis, conjunctivitis, skin allergic diseases and anaphylaxis was 26.2%, 20.0%, 14.8% and 1.1%, respectively. Sensitization to inhalant allergens was documented in 49.0% of athletes, being 32.7% in 2000 and 56.5% in 2008 (P < 0.0001). Food, drug and venom allergy was present in 7.1%, 5.0% and 2.1% of athletes, respectively. The high prevalence of asthma and allergy was associated with recurrent upper respiratory tract (10.3%) and herpes (18.2%) infections, an abnormal T cell subset profile and a general down-regulation of serum cytokines with a significantly lower IFN-γ/IL-4 ratio. CONCLUSION: A chronic and intense physical exercise may cause a transient immunodepression with a preferential shift to a Th2 response, associated with abnormalities of the respiratory tract

Guidelines for the use of flow cytometry and cell sorting in immunological studies

International audienceThe classical model of hematopoiesis established in the mouse postulates that lymphoid cells originate from a founder population of common lymphoid progenitors. Here, using a modeling approach in humanized mice, we showed that human lymphoid development stemmed from distinct populations of CD127(-) and CD127(+) early lymphoid progenitors (ELPs). Combining molecular analyses with in vitro and in vivo functional assays, we demonstrated that CD127(-) and CD127(+) ELPs emerged independently from lympho-mono-dendritic progenitors, responded differently to Notch1 signals, underwent divergent modes of lineage restriction, and displayed both common and specific differentiation potentials. Whereas CD127(-) ELPs comprised precursors of T cells, marginal zone B cells, and natural killer (NK) and innate lymphoid cells (ILCs), CD127(+) ELPs supported production of all NK cell, ILC, and B cell populations but lacked T potential. On the basis of these results, we propose a "two-family" model of human lymphoid development that differs from the prevailing model of hematopoiesis