Ketotifen inhibits tumor necrosis factor alpha production in the peripheral blood mononuclear cells of patients infected with human immunodeficiency virus

Compared with healthy individuals, patients infected with human immunodeficiency virus (HIV) have elevated levels of tumor necrosis factor alpha (TNF- alpha ). This cytokine is a powerful stimulator of HIV replication via NF- Kappa B, and the detectable plasma levels play a critical role in the development of TNF- alpha -related symptoms, such as the HIV wasting syndrome, and the clinical stages of acquired immunodeficiency syndrome. Ketotifen [4,9-dihydro-4-(1-methyl-4-piperidinylidene) -10-H-benzo[4,5]cyclohepta[1, 2-b]thiophen-10-one] is a potent antihistamine with strong H sub(1) receptor blocking activity recently introduced for the prophylaxis of asthma. In vitro, ketotifen inhibits the liberation and secretion of TNF- alpha from the peripheral blood mononuclear cells (PBMC) of both healthy individuals and HIV-infected patients. This effect was observed with PBMC in short-term culture in the presence of different mitogens and after specific stimulation of monocytic cells by CD15 monoclonal antibodies. A significant reduction in the production of TNF- alpha was obtained with nontoxic concentrations (up to 25 mu g/ml) of ketotifen.