Apoptosis of eosinophils and lymphocytes in allergic inflammation.

A characteristic feature of apoptosis is that the cellular contents that are biologically active are always surrounded by the cell membrane throughout the entire process. Thus the apoptotic cells are eliminated calmly and quickly without evoking inflammation. In allergic inflammation activated eosinophils and lymphocytes have been known to accumulate at the site of inflammation at least in part because of their prolonged survival. Corticosteroids are the most potent anti-inflammatory agent used for treating asthma. They inhibit the prolonged survival of eosinophils and lymphocytes directly by inducing apoptosis and indirectly by suppressing the release of cytokines supporting their survival. Theophylline, a classical bronchodilator, has been reported to have anti-inflammatory effects. Surprisingly, theophylline inhibited the prolonged survival of eosinophils in the presence of IL-5 in vitro by means of induction of apoptosis. Lymphocytes also undergo apoptosis in the presence of theophylline. One of the mechanisms for theophylline to induce apoptosis in eosinophils and lymphocytes is to elevate intracellular cyclic adenosine monophosphate because phosphodiesterase inhibitors and adenylate cyclase activators, which increase intracellular cyclic adenosine monophosphate, can cause apoptosis in those cells. Induction of apoptosis is beneficial in allergic inflammation, and the use of corticosteroids and theophylline in combination may be appropriate to induce apoptosis in eosinophils and lymphocytes.