Update on cytokines

Cytokines that are important in the pathophysiology of allergic disorders are summarized on Table V. The IgE isotype switch results from the activities of IL-4 and IL-13 and is inhibited by IFN-γ and TGF-β. IL-2, IL-5, and IL- 6 synergize with IL-4 and IL-13 to enhance IgE secretion. IL-4 is responsible for the differentiation of IL-4-producing lymphocytes, whereas IL-12 inhibits the differentiation of IL-4-producing T cells. IL-5 is the most important eosinophilopoietin, and together with GM-CSF and IL-3, prolongs the survival of and activates mature eosinophils. These three cytokines are responsible for the generation of the hypodense eosinophils, which characterize the asthmatic state. Eosinophilia may also result from selective recruitment by the eosinophil chemotactic factors RANTES, MIP-1α, and eotaxin. Mast cell proliferation results from the activities of IL-3, IL-9, IL-10, nerve growth factor, and stem cell factor. Finally, several cytokines contribute to the inflammatory state of allergic disorders. IL-1, TNF, and IFN-γ increase expression of endothelial cell adhesion molecules and support the egress of mononuclear cells, neutrophils, and eosinophils into the lungs. Induction of vascular cell adhesion molecule-1 by IL-4 may promote the selective recruitment of eosinophils, basophils, and lymphocytes. Many cytokines may then contribute to the activation of these leukocytes once they have reached the airways.