Adrenomedullin suppresses interleukin-1 beta-induced tumor necrosis factor-alpha production in Swiss 3T3 cells

We demonstrated that adrenomedullin (AM) inhibited interleukin-1 beta-induc ed tumor necrosis factor-alpha (TNF-alpha) secretion and gene transcription in Swiss 3T3 fibroblasts maximally to 23% and 18% of control, while the ot her peptides elevating intracellular cAMP levels elicited much weaker effec ts. AM rapidly reduced the gene transcript level of TNF-alpha, inducing a m aximal effect within 1 h, The inhibitory effect of AM was restored with an AM receptor antagonist as well as a cAMP-dependent protein kinase inhibitor , These findings indicate that AAI is a potent and quick suppressor of TNF- alpha production in Sn iss 3T3 cells acting through the cAMP protein kinase A pathway. As TNF-alpha is a major inflammatory cytokine and stimulates AM production in fibroblasts, AM is deduced to be an autocrine or paracrine f actor suppressing inflammation through the inhibition of TNF-alpha producti on. (C) 1999 Federation of European Biochemical Societies.