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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/17948

Title: Modulation of bacterial growth by tumor necrosis factor-alpha in vitro and in vivo
Authors: Lee, JH
Del Sorbo, L
Khine, AA
de Azavedo, J
Low, DE
Bell, D
Uhlig, S
Slutsky, AS
Zhang, H
Department: St. Michael's Hospital
Keywords: cytokines
phagocytosis
neutrophils
lung
transgenic/knockout
Issue Date: 15-Dec-2003
Publisher: American Thoracic Society
Citation: Lee JH et al. Modulation of bacterial growth by tumor necrosis factor-alpha in vitro and in vivo. Am J Respir Crit Care Med. 2003;168(12):1462-70.
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.
URI: http://dx.doi.org/10.1164/rccm.200302-303OC
http://hdl.handle.net/1807/17948
ISSN: 1073-449X
Appears in Collections:Faculty Publications

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