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Objective: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with an inflammatory response caused by contact of blood with artificial surfaces of the extracorporeal circuit, ischemia-reperfusion injury, and release of endotoxin. The inflammatory reaction involves activation of complement leucocytes, and endothelial cells with secretion of cytokines, proteases, arachidonic acid metabolites, and generation of oxygen derived free radicals (OFR) by polymorphonuclear neutrophils (PMN). Although this inflammatory response to CPB often remains at subclinical levels, it can also lead to major organ dysfunction. A number of studies have demonstrated that treatment of patients with a high-dose (30mg/kg) of corticosteroids (methylprednisolone) attenuates the CPB-induced SIR and improves the outcome of patients undergoing cardiac surgery. However, large doses of steroids can cause abnormal metabolic responses such as metabolic acidosis and hyperglycemia. In the present study, we examined the efficacy of low doses of methylprednisolone (5 and 10mg/kg) to attenuate the CPB-induced inflammatory response, during and after heart operations. Methods: Thirty-six adult patients undergoing cardiac surgery, were randomized into three groups: (1) control group: group A; (2) methylprednisolone, 5mg/kg body weight: group B; and (3) methylprednisolone, 10mg/kg body weight: group C. Plasma levels of the cytokines interleukin-6 (IL-6) and TNF-α were analyzed by enzyme-linked immunosorbent assay, before, during, and after CPB. OFR production was determined by cytofluorometry (FACS) at the same end points. Results: No significant differences in age, body weight, CPB time, and cross-clamp time were observed among the three groups. CPB induced a marked increased in cytokine release and OFR generation. Low-dose of methylprednisolone (5mg/kg) effectively reduced the increase in TNF-α and IL-6 secretion (P<0.05 compared to control group) after release of the cross-clamp. However, OFR generation was significantly reduced with a greater dose of methylprednisolone (10mg/kg). Conclusions: The results indicate that a single low-dose of methylprednisolone (10mg/kg) reduces the inflammatory reaction during and after CPB, by inhibition of proinflammatory cytokine release and OFR generation after release of the aortic cross-clamp. [Copyright &y& Elsevier]