Prostaglandins. Their potential in clinical medicine

The physiologic role of the prostaglandins is complex and not yet defined precisely. Nevertheless, these ubiquitous compounds do appear important to regulation of cell function and host defenses. The therapeutic potential of the prostaglandins seems to be immense, and their use in a wide variety of clinical conditions is just beginning. Whether they will also prove helpful clinically as modulators of the immune response is not clear. It is likely that an appropriate balance of prostaglandin endoperoxides, thromboxanes, prostacyclins, and probably the stable prostaglandins themselves is important to physiologic regulation of many organ systems and of immunologic reactions. Thus, development of drugs that selectively inhibit one or another of the prostaglandins and their allied compounds may prove fruitful in treatment of many diseases, including those associated with disordered immunity and tissue injury. Prostaglandin therapy in such diseases must proceed with caution. In recent studies addition of amantadine to prostaglandin E (PGE) treatment of NZB/W mice not only increased survival of these animals, but prevented development of circulating antibodies to nuclear constituents including native DNA. The results are encouraging, but must be balanced against the observation that deprivation of prostaglandin precursors also prevented nephritis and markedly increased surival of lupus mice. However, prostaglandins might be useful in a disorder whose course is more easily monitored than that of systemic lupus erythematosus: cutaneous vasculitis. The studies in which even oral administration of a PGE1 derivative suppressed immune complex-induced vasculitis (reversed passive Arthus reaction in rat skin) suggest that a trial of PGE1 treatment of cutaneous vasculitis would not be unreasonable.