Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023241 (Legionella)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor necrosis factor (TNF) was found in the lung lavage fluids of Legionella pneumophila-infected mice within 24 hr of intratracheal (i.t.) inoculation. Since this cytokine has been reported to activate polymorphonuclear leukocyte (PMN) function, the effect of TNF on the in vitro bactericidal capacity of PMN-enriched cultures was determined. Murine thioglycollate-elicited PMN which were treated with recombinant human TNF demonstrated augmented killing of L. pneumophila bacteria in vitro. Furthermore, treatment of PMN suspensions with cytokine-containing lung lavage fluid was found to enhance the bactericidal activity of PMN. The addition of anti-cachectin/TNF antibodies partially abrogated the stimulatory effects of the lavage fluid, suggesting that in vivo activation of PMN during the course of infection was likely, and that TNF was partially responsible for the enhanced bactericidal activity. In vivo treatment of animals with TNF resulted in significant protection of the animals from mortality. Furthermore, the rate of clearance of bacteria from the lung tissues of infected mice was increased in those animals treated with TNF, and correlated with the ability of this cytokine to protect the animals. These data suggest that the induction of TNF by Legionella bacteria during infection are involved in the non-specific host defense mechanisms, and that PMN activated by the TNF may be instrumental in clearing the organism from infected lung tissues, thereby protecting the animal.
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PMID:Protective effects of tumor necrosis factor in experimental Legionella pneumophila infections of mice via activation of PMN function. 316 17

Tumor necrosis factor-alpha (TNF-alpha) has been shown to stimulate the resistance of alveolar macrophages and neutrophils to Legionella pneumophila in vitro. To determine whether endogenous TNF-alpha is necessary for host defense against legionellosis in vivo, anti-TNF-alpha IgG or control IgG was administered to rats exposed to aerosolized L. pneumophila. Treatment with anti-TNF-alpha neutralized >90% of the intrapulmonary TNF-alpha response to infection, resulting in persistent pneumonitis and failure to clear L. pneumophila from the lungs. Depletion of TNF-alpha limited the recruitment of mononuclear cells to the lungs and resulted in a progressive increase in the proportion of alveolar macrophages that were infected; neutrophil recruitment and phagocytosis were not impaired. Both systemic and intrapulmonary IFN-gamma levels were significantly higher in rats depleted of TNF-alpha. These observations indicate that TNF-alpha is required for the prompt resolution of pneumonic legionellosis and point to a direct role for TNF-alpha in the activation of phagocytes.
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PMID:Antibody-mediated depletion of tumor necrosis factor-alpha impairs pulmonary host defenses to Legionella pneumophila. 933 61