Folic acid reverses hyper-responsiveness of LPS-induced chemokine secretion from monocytes in patients with hyperhomocysteinemia.

Abstract	Our previous study demonstrated that homocysteine (Hcy) mediated the expression and secretion of MCP-1 and IL-8 in human monocytes. In the present study, we investigated whether the responsiveness of isolated monocytes to lipopolysaccharide (LPS)-induced chemokine secretion was enhanced in patients with hyperhomocysteinemia (HHcy), and if so, whether this enhanced response could be inhibited by folic acid treatment. We studied 38 control subjects and 40 patients with HHcy. The results showed that MCP-1 secretion from isolated monocytes in response to low-dose LPS in patients with HHcy was significantly higher than that in controls. After patients with HHcy underwent low-dose folic acid treatment (0.8 mg/d) for 6 months, plasma Hcy levels were decreased and the hyper-responsiveness of MCP-1 and IL-8 secreted by isolated monocytes was significantly reversed. Furthermore, folic acid treatment at high concentrations (5 microM) significantly reduced the elevated levels of reactive oxygen species, NADPH oxidase activity and chemokines in response to Hcy in cultured human monocytes. HHcy may contribute to atherogenesis through enhancing the responsiveness of monocytes to inflammatory stimuli and promoting leukocyte recruitment into atherosclerotic plaque. In addition to lowering the plasma levels of Hcy, low-dose folic acid treatment exerts beneficial effects on patients with HHcy by inhibiting pro-inflammatory responses such as chemokine secretion from human monocytes.
Authors	Guang Wang, Jing Dai, Jieming Mao, Xiaokun Zeng, Xiaoda Yang, Xian Wang
Journal	Atherosclerosis (Atherosclerosis) Vol. 179 Issue 2 Pg. 395-402 (Apr 2005) ISSN: 0021-9150 [Print] Ireland
PMID	15777559 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Chemokines Hematinics Lipopolysaccharides Folic Acid NADPH Oxidases
Topics	Arteriosclerosis (drug therapy, immunology) Case-Control Studies Cell Culture Techniques Chemokines (metabolism) Folic Acid (pharmacology) Hematinics (pharmacology) Humans Hyperhomocysteinemia Inflammation Lipopolysaccharides (pharmacology) Monocytes (physiology) NADPH Oxidases (pharmacology)

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