REGULATION OF IGE AND CYTOKINE PRODUCTION BY CAMP - IMPLICATIONS FOR EXTRINSIC-ASTHMA

Recent investigations indicate that pharmacologic agents which elevate intracellular levels of cyclic AMP (cAMP) also enhance immunoglobulin E (IgE) production, This review proposes that elevation of intracellu lar cAMP is a prominent mechanism which enhances IgE production, Enhan cement is mediated by two mechanisms, First, cAMP-elevating agents dir ectly target B lymphocytes, promoting recombination of the Ig heavy ch ain loci. Second, these agents indirectly promote IgE production by in ducing a T-helper type 2 (Th2) profile of cytokine secretion. In turn, Th2-type cytokines interact with B lymphocytes and direct isotype swi tching to the epsilon locus. One type of cAMP-elevating agents, the be ta(2)-adrenergic receptor agonists (beta(2)-agonists), are used to tre at asthma. A number of detrimental phenomena have been associated with beta(2)-agonist use such as, rebound hyperresponsiveness and increase s in asthma mortality, This review theorizes that beta(2)-agonists enh ance IgE and Th2 cytokine production and that these mediators exacerba te extrinsic, IgE-dependent asthma. (C) 1996 Academic Press, Inc.