title: Upregulation of p75 tumor necrosis factor alpha receptor in Mycobacterium avium-infected mice: evidence for a functional role.
abstract: The bacterial growth and the production of tumor necrosis factor alpha (TNF-alpha) and TNF receptors (TNF-Rs) in the spleen and blood of BALB/c mice challenged with Mycobacterium avium complex (MAC) were monitored. Infection developed in two phases: the first, up to day 21, was associated with rapid MAC multiplication in the spleen and a drop in the mycobacteremia, and the second was associated with control of the infection in both compartments. In the spleen, TNF-alpha and TNF-RII mRNA levels peaked on day 21 and then slowly decreased; however, no increase in the level of TNF-RI mRNA was observed throughout these experiments. The level of circulating soluble TNF-RII (sTNF-RII) was transiently increased after day 21. In a model in which overproduction of bioactive TNF-alpha was triggered in response to a second infection with MAC, an increased production of sTNF-RII by cultured splenocytes was also observed. Administration of an antagonist anti-TNF-RII monoclonal antibody (MAb 6G1) to infected mice inhibited the bacterial growth in the spleen, suggesting that the TNF-RII and/or sTNF-RII was functionally involved in the mechanisms that control the infection. Overall, these observations suggest that upregulation of TNF-RII or sTNF-RII contributes to modulation of the TNF-alpha antibacterial activity in MAC infections.
authors.affiliation: DIBIT, San Raffaele H Scientific Institute, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Corti
authors.forename: L
authors.initials: L
authors.lastname: Fattorini
authors.forename: O F
authors.initials: OF
authors.lastname: Thoresen
authors.forename: M L
authors.initials: ML
authors.lastname: Ricci
authors.forename: A
authors.initials: A
authors.lastname: Gallizia
authors.forename: M
authors.initials: M
authors.lastname: Pelagi
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: G
authors.initials: G
authors.lastname: Orefici
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000096:biosynthesis* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009162:Mycobacterium avium; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis* / Q000276:immunology; D047889:Receptors, Tumor Necrosis Factor, Type II; D014376:Tuberculosis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha