| First Author | Wayte J | Year | 1993 |
| Journal | Crit Care Med | Volume | 21 |
| Issue | 8 | Pages | 1207-12 |
| PubMed ID | 8339588 | Mgi Jnum | J:14802 |
| Mgi Id | MGI:62963 | Doi | 10.1097/00003246-199308000-00022 |
| Citation | Wayte J, et al. (1993) Observations on the role of tumor necrosis factor-alpha in a murine model of shock due to Streptococcus pyogenes. Crit Care Med 21(8):1207-12 |
| abstractText | OBJECTIVE: To examine the effect of a monoclonal antibody to tumor necrosis factor-alpha (TNF-alpha) 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 Gram-positive shock using S. pyogenes, associated with the presence of significant concentrations of TNF-alpha in the circulation. Prophylactic administration of antibody with concomitant saline controls. A 500-micrograms 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 10(8) colony-forming units/mL of S. pyogenes H250 to mice resulted in 90% to 100% mortality rates in 72 hrs. Serum TNF-alpha concentrations peaked at 2 hrs after bacterial challenge and were 67.7 +/- 18.6 ng/mL. Treatment with anti-TNF-alpha monoclonal antibody abolished the serum TNF-alpha concentrations but did not affect the mortality rate. Serum endotoxin concentrations were < 50 pg/mL before challenge and at 0.5, 1, 2, 5, and 24 hrs after challenge. CONCLUSIONS: Pretreatment with an anti-TNF monoclonal antibody was not protective in this model of S. pyogenes sepsis, despite the presence of significant amounts of TNF in the circulation. These data suggest that TNF-alpha may not play such a crucial role in the pathogenesis of shock due to S. pyogenes. |
