Peripheral blood mononuclear cells from severe asthmatic children release lower amounts of IL-12 and IL-4 after LPS stimulation

Abstract

IntroductionAsthma is an inflammatory disorder of the airways associated with bronchial hyperresponsiveness, airway obstruction, and increased mucus production, with a predominance of type 2 immune response (Th2). According to the hygiene hypothesis, exposure to environmental bacterial lipopolysaccharide (LPS) may induce a type 1 immune response (Th1), modulating the development of asthma. ObjectiveIn this study we investigated cytokine production by peripheral blood mononuclear cells (PBMC) from children and adolescents with severe asthma, in response to LPS stimulation in vitro. Materials and methods26 children were selected: 13 severe asthmatics and 13 healthy controls, aged between 5 and 18 years. They were evaluated through routine medical history, physical examination and lung function test to diagnose severe asthma. Allergy status was confirmed by skin prick test and specific IgE assay. We collected blood samples to analyse in vitro LPS-induced cytokines release by PBMC. ResultsPBMC from severe asthmatic children produced lower levels of IL-12p70 in basal conditions and after 12 and 24h stimulation with LPS compared to healthy controls. PBMC from severe asthmatic children produced lower levels of IL-4 after 24h LPS stimulation compared to healthy controls. PBMC from severe asthmatic children produced more levels IL-17 and IL-10 after stimulus with LPS compared to healthy controls. The release of IFN-γ, IL-5 and TNF-α by PBMC from severe asthmatic children was similar to healthy controls. ConclusionOur results demonstrate that LPS directly influence the cytokine profile of PBMC in children with severe asthma. These observations may be potentially helpful in developing new treatment strategies.