Oxidative microenvironment exerts an opposite regulatory effect on cytokine production by Th1 and Th2 cells

Abstract Oxidative stress occurs in allergic disorders and immunologic inflammatory responses and reactive oxygen metabolites have an additional role of cell-signaling mediators, influencing many biological processes. Using in vitro derived Th1 and Th2 clones or T cells derived from autoimmune thyroiditis we study the ability of Th1 or Th2 cells to expand and produce cytokine in an oxidative environment. We found that low-doses of H 2 O 2 reduce the INF-γ production of activated Th1 clones and potentate the IL-4 secretion of activated Th2 clones. These effects were not due to altered cell proliferation and are not transient, since the modified secretion profile was still retained after 1 week from H 2 O 2 stimulation by both Th1 and Th2 cells. H 2 O 2 influence the profile of cytokine secretion in both Th1 and Th2. These effects are long lasting and are the result of an action of H 2 O 2 on T cell. In conclusion we demonstrate that oxidative stress plays an important role in the pathogenesis of allergic respiratory diseases and can up-regulate Th2-driven inflammation, thus contributing to increase disease severity, bronchial hyper-responsiveness and airway remodeling.