Upregulation of p75 tumor necrosis factor alpha receptor in Mycobacterium avium-infected mice: Evidence for a functional role

The bacterial growth and the production of tumor necrosis factor alpha (TMF -alpha) and TNF receptors (TNF-Rs) in the spleen and blood of BALB/c mice c hallenged 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-RT mRNA was obse rved throughout these experiments, The level of circulating soluble TNF-RII (sTNF-RII) was transiently increased after day 21, In a model in which ove rproduction of bioactive TNF-alpha was triggered in response to a second in fection with MAC, an increased production of sTNF-RII, by cultured splenocy tes was also observed. Administration of an antagonist anti-TNF-RII monoclo nal antibody (MAb 6G1) to infected mice inhibited the bacterial growth in t he spleen, suggesting that the TNF-RII and/or sTNF-RII was functionally inv olved in the mechanisms that control the infection. Overall, these observat ions suggest that upregulation of TNF-W or sTNF-RII contributes to modulati on of the TNF-alpha antibacterial activity in MAC infections.