Role of cytokines in allergic inflammation.

Moderately severe to severe allergic diseases are associated with subacute or chronic inflammation in target tissues (ie. skin or respiratory tract). Prominent cells are mast cells, eosinophils and basophils, macrophages and Th2 cells. Recent results have shown thar the main factors responsible for the inflammatory reaction are cytokines produced by the cells recruited and activated by repeated allergenic exposure: thus, the expression and/or pro duction of proinflammatory cytokines is significantly increased in allergic patients, and is correlated with the severity of the allergic disease. Pro inflammatory cytokines, such as IL-3, IL4, IL-5, and GM-SCF, act as growth and differenciation factors for mast cells and basophils, eosinophils, neut rophils, macrophages and T cells, either in bone marrow, lymphoid organs, o r in inflamed tissues themselves. Moreover, most cytokines produced by thes e cells, such as IL-6, IL-8, IL-10, IL-13, MIP and MCP, RANTES and TNF-alph a, induce intercellular adhesion molecules on endothelial and effector cell s, and promote extravasation of effector cells in inflamed tissues. These c ytokines also induce or promote activation of the effector cells themselves , leading to the production of vasoactive, bronchoconstrictor, and chemotac tic mediators, such as prostaglandins, thromboxanes, leukotrienes and PAF. In turn, these mediators activate the effector cells, leading to increased production of proinflammatory cytokines. In normal subjects, the effects of proinflammatory cytokines are controlled by soluble receptors, receptor an tagonists, such as IL-1Ra, and anti-inflammatory cytokines. In allergic pat ients, the production of these regulatory factors is deficient, especially during allergen exposures. Finally, specific immunotherapy (SIT) induces no rmalization of the Th1/Th2 response responsible for decreased IgE productio n and increased IgG (4) production. Moreover, SIT decreases the production of proinflammatory cytokines and increases the production of anti-inflammat ory cytokines, leading to a significant reduction in the number and activab ility of effector cells in blood and target tissues.