Regulation of tumour necrosis factor production by mouse peritoneal macrophages: the role of cellular cyclic AMP.

Abstract

We have studied the role of cyclic adenosine 3':5' monophosphate (cAMP) in the regulation of lipopolysaccharide (LPS)-induced tumour necrosis factor (TNF) production by mouse peritoneal macrophages. LPS did not alter the intracellular levels of cAMP. However, prostaglandin E2 (PGE2) and cholera toxin, both of which are known to increase intracellular levels of cAMP, consistently inhibited LPS-induced TNF production. The cAMP analogues, dibutyryl cAMP (DbcAMP) and 8-bromo cAMP (8BrcAMP), also inhibited TNF production, whereas pertussis toxin, which inactivates the inhibitory guanine nucleotide-binding protein (Gi), had no effect. These observations suggested that LPS did not itself modify macrophage adenylate cyclase activity, while agents that increased intracellular cAMP levels were able to inhibit LPS-induced macrophage TNF production.