European Cytokine Network


Anti-inflammatory response after infusion of p55 soluble tumor necrosis factor receptor fusion protein for severe sepsis Volume 14, issue 1, March 2003


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Division of Surgical Intensive Care, Department of Anesthesiology, Pharmacology and Surgical Intensive Care, Geneva University Hospital, 1211 Geneva 14, Switzerland.

Objectives: To investigate the effects of Lenercept®, a recombinant soluble TNF receptor p55 fused to an immunoglobulin heavy chain IgG1, on the balance of pro- and anti-inflammatory mediators in sepsis. Design: Post hoc analysis of a subgroup of patients enrolled in a multicenter phase III, prospective, double-blind, placebo-controlled, randomized study of Lenercept® in severe sepsis. Setting: Surgical and medical intensive care units, and postoperative recovery room of a tertiary care teaching hospital. Patients: A total of 57 patients were enrolled in the multicenter study in our center. Intervention: Septic patients were randomly assigned to receive either Lenercept® 0.125 mg/kg or placebo. The patients were followed for up to 28 days after randomization. Measurements and main results: Circulating levels of TNF-alpha, IL-6, TNFsR75 and IL-1Ra were measured before and after treatment. The two groups were comparable with regard to age, gender and diagnosis distribution. The total level of TNF-alpha increased significantly in treated patients, compared to patients receiving placebo. The levels of the other inflammatory mediators did not differ between the two groups Conclusions: Lenercept®-treated patients experienced a protracted TNF-alpha half-life, leading to higher total TNF-alpha levels throughout the study. However, the treatment had no effects on anti-inflammatory mediators. Therefore, peripheral inflammatory processes might not have been significantly modified by the treatment. This might account for the lack of efficacy this treatment in septic patients