Monoclonal Antibody to Endotoxin Core Protects Mice from Escherichia coli Sepsis by a Mechanism Independent of Tumor Necrosis Factor and Interleukin-6

• Published in: The Journal of infectious diseases Vol. 162; no. 2; pp. 454 - 459
• Main Authors: Silva, Ayona T., Appelmelk, Ben J., Buurman, Wim A., Bayston, Katherine F., Cohen, Jonathan
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01-08-1990; University of Chicago Press
• Subjects: Animals; Antibodies; Antibodies, Monoclonal - therapeutic use; Bacteriology; Biological and medical sciences; Blood; Cytokines; Disease Models, Animal; Endotoxins; Endotoxins - immunology; Escherichia coli Infections - etiology; Escherichia coli Infections - prevention & control; Fundamental and applied biological sciences. Psychology; Immunization, Passive; Interleukin-6 - analysis; Interleukin-6 - biosynthesis; Major Articles; Male; Mice; Microbiology; Monoclonal antibodies; Necrosis; Sepsis; Septic shock; Shock, Septic - etiology; Shock, Septic - prevention & control; Tumor Necrosis Factor-alpha - analysis; Tumor Necrosis Factor-alpha - biosynthesis; Tumor necrosis factors; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Immunoprotection; Vertebrata; Experimental disease; Mammalia; Mouse; Escherichia coli; Rodentia; Cytokine; Bacteria; Monoclonal antibody; Endotoxin; Enterobacteriaceae
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/162.2.454

To study the role of cytokines as mediators of endotoxin-induced shock, the serum levels of tumor necrosis factor (TNF) and interleukin-6 (IL-6) were compared in mice receiving either a monoclonal antibody to endotoxin core (clone 20), an irrelevant monoclonal antibody (A1), or culture media (DMEM/FCS) alone before lethal challenge with live Escherichia coli 0111:B4. Clone 20 given 1.5 h before the bacterial challenge protected mice from death (mortality at 48 h 3% vs. 87%, P < .001). The pattern of IL-6 release was indistinguishable in clone 20 recipients and controls: The area under the curve (AVC) for 5 h was 1.22 ± 0.07 × 106, 1.03 ± 0.17 × 106, and 1.22 ± 0.07 × 106 units/ml for clone 20, Al, and DMEM/FCS, respectively. Similarly, the timing and extent of TNF release in the serum was virtually identical in clone 20 recipients that survived and control animals that died. AVC for 5 h was 30.8 ± 4.0 × 103, 28.1 ± 1.1 × 103, and 30.4 ± 4.7 × 103 ng/ml in clone 20, A1, and DMEM/FCS recipients, respectively. Thus, TNF and IL-6 appear insufficient to cause death in this model ofexperimental gram-negative shock.