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 beta2-adrenergic receptor agonists (beta2-agonists), are used to treat asthma. A number of detrimental phenomena have been associated with beta2-agonist use such as, rebound hyperresponsiveness and increases in asthma mortality. This review theorizes that beta2-agonists enhance IgE and Th2 cytokine production and that these mediators exacerbate extrinsic, IgE-dependent asthma.
Fedyk
E R
ER
Immunology Program of the Cancer Center, University of Rochester School of Medicine and Dentistry, New York 14642, USA.
Adawi
A
A
Looney
R J
RJ
Phipps
R P
RP
D000818:Animals; D001249:Asthma / Q000503:physiopathology; D000242:Cyclic AMP / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D007073:Immunoglobulin E / Q000502:physiology*
D016207:Cytokines; D007073:Immunoglobulin E; D000242:Cyclic AMP