The Cyclooxygenase-2 Theory of Atopy and Asthma

Abstract

The prevalence of allergic disorders, and in particular asthma, appears to be increasing in Western societies. Medications can control the symptoms of allergic disease and asthma but a better understanding of the pathophysiologic mechanisms is needed to develop new therapies, in particular for viral-induced exacerbations of asthma, as well as effective methods of primary prevention. The cyclooxygenase-2 (COX-2) theory of atopy and asthma is based upon viewing the TH₁/TH₂ paradigm of immune responses as a dynamic process, particularly in regard to the innate immune response to respiratory viral infection. Recent data suggests that prostaglandin E₂ (PGE₂) inhibits lymphocyte production of TH₁ type cytokines IL-2 and IFN-γ, but enhances production of the TH₂ cytokines IL-4 and IL-5. COX-2, as opposed to the constitutively expressed cyclooxygenase-1 enzyme, is thought to be responsible for PGE₂ generation during acute inflammation. During a viral respiratory infection, COX-2 is activated but maximal production of PGE₂ is delayed, which leads to inhibition of acute antiviral TH₁-like cytokines and the induction of TH₂ cytokines. TH₂ cytokines, particularly IL-4, then inhibit COX-2, leading to the final resolution of the acute inflammatory process. Altered regulation of activation or inhibition of COX-2 in those with an atopic predisposition may therefore be responsible for the development of allergic diseases.