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


METHODS
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.


METHODS
Surgical and medical intensive care units, and postoperative recovery room of a tertiary care teaching hospital.


METHODS
A total of 57 patients were enrolled in the multicenter study in our center.


METHODS
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.


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
Butty
Vincent L
VL
Department of Anesthesiology, Pharmacology and Surgical Intensive Care, Geneva University Hospital, 1211 Geneva 14, Switzerland.
Roux-Lombard
Pascale
P
Garbino
Jorge
J
Dayer
Jean-Michel
JM
Ricou
Bara
B
D016207:Cytokines / Q000097:blood*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007143:Immunoglobulin Heavy Chains; D007142:Immunoglobulin gamma-Chains; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D010919:Placebos; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D018805:Sepsis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D012772:Shock, Septic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D016207:Cytokines; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007142:Immunoglobulin gamma-Chains; D010919:Placebos; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; C099374:Ro 45-2081