Soluble tumour necrosis factor (TNF)-receptor levels in serum as markers of anti-viral host reactivity

The role of soluble receptors for TNF-alpha (sTNF-Rs) as markers of virus-i nduced host responses was studied by the use of murine model infections. A marked elevation in serum levels of sTNF-R75, but not sTNF-R55, was found 1 day after infection with vesicular stomatitis virus (VSV). In mice infecte d with lymphocytic choriomeningitis virus (LCMV), an early increase was als o revealed, but peak levels of sTNF-R75 were observed later temporally rela ted to maximal T cell-mediated anti-viral activity. Analysing different wel l characterized knockout mice, it was found that elevated release of sTNF-R 75 into serum early after VSV infection was independent of T cells, whereas interferon (IFN)-alpha/beta seemed to be a major mediator. In contrast, in creased release of sTNF-R75 into serum 8 days post-LCMV infection was media ted via T cells but independently of both CD40 ligand and IFN-gamma. A simp le correlation between release of sTNF-Rs in vivo and macrophage activation in vitro was not present. These findings indicate that sTNF-R75 is indeed a sensitive marker of both innate and specific cell-mediated host reactivit y during viral infection, but it is not correlated to a single immunologica l parameter.