Prophylactic and therapeutic effects of a monoclonal antibody to tumor necrosis factor-alpha in experimental gram-negative shock.
A monoclonal antibody to recombinant murine tumor necrosis factor-alpha (TNF alpha), TN3-19.12, was used to explore pathogenetic mechanisms and therapeutic strategies in gram-negative shock. In mice receiving an LD90 dose of Escherichia coli O111, TN3-19.12 prevented death if given 1.5 h before or 30 min after challenge. Less protection was conferred if the antibody was given 2.5 h after challenge. In control mice receiving an irrelevant antibody, L2-3D9, TNF alpha levels rose (less than or equal to 185.1 +/- 26.1 ng/ml) by 90 min and had returned to baseline by 5 h. Mice receiving TN3-19.12 did not have this response. TN3-19.12 was of limited benefit in mice receiving Pseudomonas aeruginosa but had no protective effect in cyclophosphamide-treated mice receiving Klebsiella pneumoniae. In L2-3D9-treated mice, TNF alpha levels were elevated to 61.8 +/- 27.9 and 49.7 +/- 5.1 ng/ml by 90 min in the two models, respectively. TNF alpha levels in TN3-19.12-treated mice in these two models were very low (3.9-5.5 ng/ml). TNF alpha is a mediator in gram-negative shock; antibody to TNF alpha can be of value in prophylaxis and treatment, but its clinical use remains to be established.
Silva
A T
AT
Department of Bacteriology, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
Bayston
K F
KF
Cohen
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004756:Enterobacteriaceae Infections / Q000150:complications; D006090:Gram-Negative Bacteria; D007116:Immunization, Passive; D007165:Immunosuppression Therapy; D008297:Male; D051379:Mice; D011552:Pseudomonas Infections / Q000150:complications; D018805:Sepsis / Q000150:complications*; D012772:Shock, Septic / Q000517:prevention & control* / Q000628:therapy; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology*; D015431:Weight Loss
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha