Pro-inflammatory action of LDL(-) on mononuclear cells is counteracted by increased IL10 production

Objective: LDL(-) is a minor LDL subfraction that induces inflammatory factor release by endothelial cells. Since LDL(-) is present in plasma, its interaction with leucocytes, a cell type involved in atherosclerosis phenomena, is feasible; therefore, the aim of the current study was to evaluate LDL(-) effect on lymphocytes and monocytes isolated from human plasma. Methods and Results: Mononuclear cells were incubated with LDL(+) and LDL(-) and expression and release of several inflammatory mediators were analyzed by protein membrane assay, ELISA and real-time RT-PCR. LDL(-) induced a significantly increased production versus LDL(+) in MCP1, GRO beta, GRO gamma, IL6, IL8 and IL10 in monocytes as well as in lymphocytes. These induced molecules are inflammatory, except for IL10 which is considered an anti-inflammatory cytokine. Therefore, the role of IL10 was evaluated in experiments where exogenous IL10 or antibodies anti-IL10 or anti-IL10 receptor were added. IL10 addition diminished the release of the other factors induced by LDL(-) near to basal production both at protein and RNA level. In contrast, the antibody anti-IL 10 increased inflammatory cytokine release around two-fold, whereas the antibody anti-IL 10 receptor produced a lower effect. Conclusions.- LDL(-) promoted inflammatory cytokine production in leucocytes; however, it also induced IL10 that minimized this effect. Therefore, IL10 developed a significant role in counteracting the LDL(-) inflammatory action. (C) 2007 Elsevier B.V. All rights reserved.