Dibutyryl cyclic AMP protects Corynebacterium parvum-treated mice against lipopolysaccharide-induced lethal toxicity

The effects of dibutyryl cyclic AMP (DBcAMP) on the lethal toxicity of lipopolysaccharide (LPS) were investigated in mice made hypersensitive to LPS by administration with Corynebacterium parvum (C. parvum). The peritoneal macrophages in C. parvum-treated mice released a conspicuous level of TNF alpha in response to LPS in vitro. These macrophages exhibited much higher susceptibility to LPS-induced cytotoxicity than with resident or peptone-induced macrophages. Pretreatment of the C. parvum-induced macrophages with DBcAMP significantly inhibited the TNF alpha production in response to LPS and decreased the susceptibility to LPS-induced cytotoxicity in vitro. Similar to the findings seen in in vitro experiments, in vivo administration with DBcAMP significantly inhibited the TNF alpha release in the sera of C. parvum-treated mice after LPS challenge and consequently decreased the susceptibility to LPS-induced shock. These results suggest that raising level of intracellular cAMP protects C. parvum-treated mice from hypersensitivity to lethal toxicity of LPS through downregulating TNF alpha synthesis.