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Submitted on August 18, 2004
Accepted on November 23, 2004
Department of Medicine, The University of Hong Kong, Hong Kong, China, Department of Physiology, The University of Hong Kong, Hong Kong, China
* To whom correspondence should be addressed. E-mail: lyfwong{at}hkucc.hku.hk.
Adrenomedullin (ADM) is a potent vasorelaxant peptide that plays important roles in cardiovascular homeostasis and inflammatory response. ADM derived from macrophages is one of the major sources of ADM which is produced in inflammatory process. To assess the functions of ADM in inflammation, we studied the temporal changes in ADM production and its effect on secretion of macrophage migration inhibitory factor (MIF) and cytokine response of NR8383 rat macrophages activated by lipopolysaccharide (LPS). NR8383 cells were stimulated by LPS in the absence and presence of exogenous ADM, and the concentrations of ADM, MIF and proinflammatory cytokines (IL-6, TNF-
and IL-1 
) in the culture media and gene expressions of the cells were measured. We confirmed that the secretion and mRNA expression of ADM in the macrophages were markedly increased by LPS. ADM increased initial secretion of MIF and IL-1 from both non-stimulated and LPS-stimulated cells, and it also increased basal and LPS-induced IL-6 secretion of the cells by 2 to 15-fold. However, it reduced secretion of TNF- from LPS-stimulated cells by 34 to 56%. Our results suggest that ADM modulates MIF secretion and cytokine production and plays important roles in both the initiation and propagation of inflammatory response.
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