Inhibition of prostaglandin E2 formation and histamine action in cancer immunotherapy.

The activity of cell-mediated defense systems is stimulated by consecutive formation of interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2) and interferon gamma (IFN gamma). The system is inhibited by interleukin-4 (IL-4) and also by prostaglandin E2 (PGE2) and histamine, which are released when the immune system is activated. The inhibition is strong in cancer patients, because PGE2 is formed in many cancer cells and its formation is stimulated by IL-1 beta. The release of histamine is also stimulated by IL-1 beta. Thus PGE2 and histamine are feedback inhibitors of cell-mediated immunity. This inhibition can be abolished by inhibitors of the cyclo-oxygenase (e.g. indomethacin) and H-2 receptor antagonists (e.g. cimetidine). This may offer a new option to stimulate the immune system to kill cancer cells.