Observations on the role of tumor necrosis factor-α in a murine model of shock due to Streptococcus pyogenes

Abstract

Objective To examine the effect of a monoclonal antibody to tumor necrosis factor-α (TNF-α) in a murine model of shock due to Streptococcus pyogenes. Design Prospective, multiexperimental, randomized, controlled trial. Setting University hospital research laboratory. Interventions An LD₉₀ murine model of Grampositive shock using S. pyogenes, associated with the presence of significant concentrations of TNF-α in the circulation. Prophylactic administration of antibody with concomitant saline controls. A 500-μg TN3–19.12 (hamster monoclonal antibody to recombinant murine TNF), or saline, by intravenous injection was administered. Measurements and Main Results Administration of 0.3 mL of 6 x 10⁸ colony-forming units/mL of S. pyogenes H250 to mice resulted in 90% to 100% mortality rates in 72 hrs. Serum TNF-α concentrations peaked at 2 hrs after bacterial challenge and were 67.7 ± 18.6 ng/mL. Treatment with anti-TNF-α monoclonal antibody abolished the serum TNF-α concentrations but did not affect the mortality rate. Serum endotoxin concentrations were S. pyogenes sepsis, despite the presence of significant amounts of TNF in the circulation. These data suggest that TNF-α may not play such a crucial role in the pathogenesis of shock due to S. pyogenes. (Crit Care Med 1993; 21:1207–1212)