Homocysteine at pathophysiologic concentrations activates human monocyte and induces cytokine expression and inhibits macrophage migration inhibitory factor expression

Objective: Homocystinemia is an important independent risk factor for atherosclerosis. Inflammatory cytokines play key roles in the development of atherogenesis. This study investigated the effect of homocysteine on inflammatory cytokine expression. Methods: Human monocytes were treated in vitro with a variety Of DL-homocysteine concentrations that ranged from physiologic concentration to higher than pathophysiologic concentration, and we analyzed their expressions of inflammatory cytokines, including tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, interleukin-8, interleukin-12, and migration inhibitory factor. Results: DL-homocysteine at a marginal physiologic concentration of 2 mu g/mL (15 mu M) activated monocytes. In addition, DL-homocysteine at the pathophysiologic dose of 25 mu g/mL (185 mu M) induced mRNA and protein expressions of inflammatory cytokines tumor necrosis factor-alpha, IL-1 beta, interleukin-6, interleukin-8, and interleukin-12. Moreover, at the larger dose of 50 mu g/mL (370 mu M) DL-homocysteine decreased expression of migration inhibitory factor at the mRNA and protein levels. Conclusion: These findings suggest that homocysteine may contribute to the initiation and progression of vascular disease by activating monocytes, resulting in the secretion of cytokines that amplify the inflammatory response. (c) 2005 Elsevier Inc. All rights reserved.