Effects of an S-adenosyl-l-homocysteine hydrolase inhibitor on murine macrophage activation and function

The S-adenosyl-l-homocysteine (AdoHcy) hydrolase inhibitor MDL 28,842 has been demonstrated to be a potent inhibitor of T-cell activation, both in vitro and in vivo. Although the inhibition of T cells in vitro was independent of macrophages, the direct effect of MDL 28,842 on macrophages is unknown. In this report the effects of MDL 28,842 on macrophage cytokine production, cell-surface antigen expression, and antigen processing and presentation were examined. Lipopolysaccharide (LPS) stimulation of IL-1 synthesis by peritoneal macrophages was not effected by MDL 28,842 using cells obtained from B10.A and B10.B mice and weakly inhibited using cells from BALB/C mice (IC50>10 μM). In contrast, TNF-α synthesis by BALB/C macrophages was inhibited by MDL 28,842 with an IC50