John Libbey Eurotext

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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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Authors
Division of Surgical Intensive Care, Department of Anesthesiology, Pharmacology, and Surgical Intensive Care Division of Immunology and Allergy and Division of Infectious Diseases, Department of Internal Medicine, University Hospital, Geneva, Switzerland

Objectives: To investigate the effects of Lenercept ®, a recombinant soluble TNF receptor p55 fused to an immunoglobulin heavy chain IgG 1, 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‐α, IL‐6, TNFsR 75 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‐α 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‐α half‐life, leading to higher total TNF‐α 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.