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

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-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

• Authors: Vincent L Butty, Pascale Roux-Lombard, Jorge Garbino, Jean-Michel Dayer, Bara Ricou, Geneva Sepsis Network
• Journal: European cytokine network (Eur Cytokine Netw) 2003 Jan-Mar Vol. 14 Issue 1 Pg. 15-9 ISSN: 1148-5493 [Print] France
• PMID: 12799209 (Publication Type: Clinical Trial, Clinical Trial, Phase III, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Immunoglobulin G
• Immunoglobulin Heavy Chains
• Immunoglobulin gamma-Chains
• Placebos
• Receptors, Tumor Necrosis Factor
• Recombinant Fusion Proteins
• Tumor Necrosis Factor-alpha
• Ro 45-2081

Topics

• Cytokines (blood)
• Double-Blind Method
• Female
• Humans
• Immunoglobulin G (therapeutic use)
• Immunoglobulin Heavy Chains
• Immunoglobulin gamma-Chains
• Intensive Care Units
• Male
• Middle Aged
• Placebos
• Receptors, Tumor Necrosis Factor (therapeutic use)
• Recombinant Fusion Proteins (therapeutic use)
• Sepsis (blood, drug therapy, immunology)
• Shock, Septic (blood, drug therapy, immunology)
• Treatment Outcome
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)