Open Access

ARTICLE

Anti-inflammatory response after infusion of p55 soluble tumor necrosis factor receptor fusion protein for severe sepsis

Vincent L. Butty¹, Pascale Roux-Lombard², Jorge Garbino³, Jean-Michel Dayer², Bara Ricou¹, and the Geneva Sepsis Network¹ (participating members are listed in the appendix)

1 Division of Surgical Intensive Care, Department of Anesthesiology, Pharmacology, and Surgical Intensive Care
2 Division of Immunology and Allergy and 3 Division of Infectious Diseases, Department of Internal Medicine, University Hospital, Geneva, Switzerland

* Corresponding Author: Bara Ricou,

European Cytokine Network 2003, 14(1), 15-19.

Abstract

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-α, 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-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-a 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.

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