Adrenaline inhibits lipopolysaccharide-induced macrophage inflammatory protein-1α in human monocytes: The role of β-adrenergic receptors

Macrophage inflammatory protein-1α (MIP-1α) 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-1α production by human peripheral blood monocytes and human monocytic THP-1 cells. Monocytes were incubated in vitro with LPS for 4 h at 37°C in the presence and absence of adrenaline and/or specific α- and β-adrenergic receptor antagonists and agonists. The effects of adrenaline on MIP-1α 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-1α production in a dose-dependent manner. The suppressive effect could be completely prevented by propranolol, but not by phentolamine. The specific β-adrenergic agonist isoproterenol produced the same inhibitory effect on LPS-induced MIP-1α production, whereas the α-adrenergic agonist phenylephrine had a minimal effect. In addition, suppression of MIP-1α 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-1α messenger RNA expression. These findings suggest that adrenaline can modulate MIP-1α production in inflammatory diseases and sepsis.