PMID- 2373872 OWN - NLM STAT- MEDLINE DCOM- 19900827 LR - 20211203 IS - 0022-1899 (Print) IS - 0022-1899 (Linking) VI - 162 IP - 2 DP - 1990 Aug TI - Prophylactic and therapeutic effects of a monoclonal antibody to tumor necrosis factor-alpha in experimental gram-negative shock. PG - 421-7 AB - 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. FAU - Silva, A T AU - Silva AT AD - Department of Bacteriology, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom. FAU - Bayston, K F AU - Bayston KF FAU - Cohen, J AU - Cohen J LA - eng GR - Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Infect Dis JT - The Journal of infectious diseases JID - 0413675 RN - 0 (Antibodies, Monoclonal) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Animals MH - Antibodies, Monoclonal/*therapeutic use MH - Colony Count, Microbial MH - Disease Models, Animal MH - Enterobacteriaceae Infections/complications MH - Gram-Negative Bacteria MH - *Immunization, Passive MH - Immunosuppression Therapy MH - Male MH - Mice MH - Pseudomonas Infections/complications MH - Sepsis/*complications MH - Shock, Septic/*prevention & control/therapy MH - Tumor Necrosis Factor-alpha/analysis/*immunology MH - Weight Loss EDAT- 1990/08/01 00:00 MHDA- 1990/08/01 00:01 CRDT- 1990/08/01 00:00 PHST- 1990/08/01 00:00 [pubmed] PHST- 1990/08/01 00:01 [medline] PHST- 1990/08/01 00:00 [entrez] AID - 10.1093/infdis/162.2.421 [doi] PST - ppublish SO - J Infect Dis. 1990 Aug;162(2):421-7. doi: 10.1093/infdis/162.2.421.