PMID- 12958055 OWN - NLM STAT- MEDLINE DCOM- 20040212 LR - 20141120 IS - 1073-449X (Print) IS - 1073-449X (Linking) VI - 168 IP - 12 DP - 2003 Dec 15 TI - Modulation of bacterial growth by tumor necrosis factor-alpha in vitro and in vivo. PG - 1462-70 AB - Tumor necrosis factor-alpha (TNF-alpha) plays an important role in innate immunity. Recent in vitro studies have shown that TNF-alpha may also serve as a growth factor for some bacteria. We examined the physiologic relevance of this phenomenon both in vitro and in vivo. Recombinant mouse TNF-alpha increased in vitro proliferation of Escherichia coli but not Pseudomonas aeruginosa in a concentration-dependent manner, and this effect was attenuated by anti-TNF-alpha antibodies. However, in vivo, TNF-alpha gene-deficient (TNF-alpha-/-) mice showed higher mortality than wild-type (TNF-alpha+/+) mice after inoculation of intranasal bacteria. An impaired bacterial clearance in TNF-alpha-/- mice was associated with decreased systemic concentrations of chemokine macrophage inflammatory protein-2, reduced pulmonary neutrophil recruitment, and depressed expression of neutrophil CD11b and CD16/CD32, suggesting that the effect of TNF-alpha on E. coli growth was outweighed by the recruited neutrophils. We also demonstrated that neutropenic TNF-alpha+/+ mice had approximately 100-fold higher E. coli counts in their lungs than TNF-alpha-/- mice, although survival rates in both groups were similar. We conclude that TNF-alpha augments E. coli growth in vitro and in vivo. However, in vivo, this effect becomes only apparent in neutropenic animals. The relevance of these findings for immune compromised patients remains to be investigated. FAU - Lee, Jin-Hwa AU - Lee JH AD - Department of Anaesthesia, St. Michael's Hospital, Toronto, ON, M5B 1W8 Canada. FAU - Del Sorbo, Lorenzo AU - Del Sorbo L FAU - Khine, Aye Aye AU - Khine AA FAU - de Azavedo, Joyce AU - de Azavedo J FAU - Low, Donald E AU - Low DE FAU - Bell, David AU - Bell D FAU - Uhlig, Stefan AU - Uhlig S FAU - Slutsky, Arthur S AU - Slutsky AS FAU - Zhang, Haibo AU - Zhang H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20030904 PL - United States TA - Am J Respir Crit Care Med JT - American journal of respiratory and critical care medicine JID - 9421642 RN - 0 (Tumor Necrosis Factor-alpha) SB - IM CIN - Am J Respir Crit Care Med. 2003 Dec 15;168(12):1410-1. PMID: 14668252 MH - Animals MH - Escherichia coli/drug effects/*growth & development MH - Immunocompromised Host/drug effects/*immunology MH - In Vitro Techniques MH - Male MH - Mice MH - Mice, Knockout MH - Neutropenia/immunology MH - Neutrophil Activation/drug effects/immunology MH - Neutrophil Infiltration/drug effects/immunology MH - Pneumonia, Bacterial/*immunology/microbiology MH - Pseudomonas aeruginosa/drug effects/*growth & development MH - Tumor Necrosis Factor-alpha/genetics/*immunology/pharmacology EDAT- 2003/09/06 05:00 MHDA- 2004/02/13 05:00 CRDT- 2003/09/06 05:00 PHST- 2003/09/06 05:00 [pubmed] PHST- 2004/02/13 05:00 [medline] PHST- 2003/09/06 05:00 [entrez] AID - 200302-303OC [pii] AID - 10.1164/rccm.200302-303OC [doi] PST - ppublish SO - Am J Respir Crit Care Med. 2003 Dec 15;168(12):1462-70. doi: 10.1164/rccm.200302-303OC. Epub 2003 Sep 4.