title: Modulation of bacterial growth by tumor necrosis factor-alpha in vitro and in vivo.
abstract: 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.
authors.affiliation: Department of Anaesthesia, St. Michael's Hospital, Toronto, ON, M5B 1W8 Canada.
authors.forename: Jin-Hwa
authors.initials: JH
authors.lastname: Lee
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Del Sorbo
authors.forename: Aye Aye
authors.initials: AA
authors.lastname: Khine
authors.forename: Joyce
authors.initials: J
authors.lastname: de Azavedo
authors.forename: Donald E
authors.initials: DE
authors.lastname: Low
authors.forename: David
authors.initials: D
authors.lastname: Bell
authors.forename: Stefan
authors.initials: S
authors.lastname: Uhlig
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Slutsky
authors.forename: Haibo
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development*; D016867:Immunocompromised Host / Q000187:drug effects / Q000276:immunology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009503:Neutropenia / Q000276:immunology; D018375:Neutrophil Activation / Q000187:drug effects / Q000276:immunology; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology
chemical_list: D014409:Tumor Necrosis Factor-alpha