Elevated levels of homocysteine increase IL-6 production in monocytic MonoMac 6 cells

Hyperhomocysteinemia is a risk factor for atherosclerosis and thrombosis. T he aim of this study was to analyze if exposure of monocytic cells to incre ased levels of homocysteine (HCY) induces the accumulation of inflammatory mediators. Interleukin (IL)-6 production by monocytic cell line Mono Mac 6 (MM6) was 1.7-fold increased in the presence of 50 mu mol/l HCY and 3.5-fol d with 200 mu mol/l HCY, Incubation with homocystine resulted in a comparab le dose-dependent increase, but neither cysteine nor methionine stimulated IL-6 accumulation. Elevated homocysteine concentrations did not affect the production of IL-8 and monocytic chemotactic protein-1 (MCP-1) in MM6. Furt hermore, lipopolysaccharide (LPS) stimulation of MM6, cultured with elevate d I-ICY (200 mu mol/l) levels, resulted in a 3.5-fold increased response af ter 18 h, whereas no effect on LPS-induced IL-8 and MCP-1 response was obse rved. In conclusion, increased concentrations of homocysteine induce IL-6 a ccumulation in monocytic cells. After treatment with homocysteine, monocyti c cells become more susceptible to endotoxin. This study is in favor of an association between homocysteine and monocytic IL-6 production. Blood Coag Fibrinol 11:159-164 (C) 2000 Lippincott Williams & Wilkins.