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 intracellular cAMP is a prominent mechanism which enhances IgE production, Enhancement is mediated by two mechanisms, First, cAMP-elevating agents directly target B lymphocytes, promoting recombination of the Ig heavy chain loci. Second, these agents indirectly promote IgE production by inducing a T-helper type 2 (Th2) profile of cytokine secretion. In turn, Th2-type cytokines interact with B lymphocytes and direct isotype switching to the epsilon locus. One type of cAMP-elevating agents, the beta(2)-adrenergic receptor agonists (beta(2)-agonists), are used to treat asthma. A number of detrimental phenomena have been associated with beta(2)-agonist use such as, rebound hyperresponsiveness and increases in asthma mortality, This review theorizes that beta(2)-agonists enhance IgE and Th2 cytokine production and that these mediators exacerbate extrinsic, IgE-dependent asthma. (C) 1996 Academic Press, Inc.