Adrenaline inhibits lipopolysaccharide-induced macrophage inflammatory protein-1 alpha in human monocytes: the role of beta-adrenergic receptors.

Abstract

Macrophage inflammatory protein-1 alpha (MIP-1 alpha) has an important role in the development of inflammatory responses during infection by regulating leukocyte trafficking and function. Our study was conducted to investigate the effect of adrenaline on lipopolysaccharide (LPS)-induced MIP-1 alpha production by human peripheral blood monocytes and human monocytic THP-1 cells. Monocytes were incubated in vitro with LPS for 4 h at 37 degrees C in the presence and absence of adrenaline and/or specific alpha- and beta-adrenergic receptor antagonists and agonists. The effects of adrenaline on MIP-1 alpha synthesis were studied at the protein level by using enzyme-linked immunosorbent assays and at the messenger RNA level by using reverse transcriptase-polymerase chain reaction. Adrenaline inhibited LPS-induced MIP-1 alpha production in a dose-dependent manner. The suppressive effect could be completely prevented by propranolol, but not by phentolamine. The specific beta-adrenergic agonist isoproterenol produced the same inhibitory effect on LPS-induced MIP-1 alpha production, whereas the alpha-adrenergic agonist phenylephrine had a minimal effect. In addition, suppression of MIP-1 alpha production was associated with an increase of intracellular cyclic adenosine monophosphate (cAMP) by the cell membrane-permeable cAMP analog dibutyryl-cAMP. Furthermore, we found that adrenaline inhibited LPS-induced MIP-1 alpha messenger RNA expression. These findings suggest that adrenaline can modulate MIP-1 alpha production in inflammatory diseases and sepsis.