The role of prostaglandins in endotoxic activities.

Endotoxins elicit an extraordinary variety of biological effects in higher organisms. Mononuclear phagocytes are believed to be the cellular source of secondary mediators responsible for the host's reaction. Several findings indicate that among these endogenous mediators prostaglandins are of importance. Macrophages of different origin synthesize prostaglandins when stimulated with LPS. The prostaglandin-inducing activity is located in the lipid A part of the LPS molecule. Macrophages from an LPS-resistant mouse strain (C3H/HeJ) and cells from mice rendered tolerant to LPS do not produce prostaglandins in vitro when incubated with LPS, a phenomenon paralleling the lack of in vivo activity. Certain prostaglandins (TxA2 and PGI2) have been shown to be of importance in endotoxicosis. We found that macrophages do not produce TxA2 and PGI2 on incubation with LPS in vitro, although they possess the potential to synthesize these metabolites. Thus it remains to be elucidated which role macrophages, their prostaglandin production and/or other factors play in endotoxicosis.