Monoclonal nonspecific suppressor factor beta (MNSF beta) inhibits the production of TNF-alpha by lipopolysaccharide-activated macrophages.

The monoclonal nonspecific suppressor factor (MNSF), a lymphokine produced by a murine T cell hybridoma, shows a pleiotropic antigen-nonspecific suppressive function. Most recently, a cDNA encoding a subunit of MNSF (MNSF beta) has been isolated and characterized. Recombinant form of MNSF beta (rMNSF beta) inhibits lymphokine functions, as does native MNSF. In this study, we investigated whether rMNSF beta also affects macrophage function in terms of LPS-induced TNF-alpha production by a mouse macrophage cell line, J774. rMNSF beta suppressed the TNF-alpha production in a dose-dependent manner. This suppressive effect was remarkably reduced when rMNSF beta was added after 6 h of LPS stimulation. In addition, enhancement of TNF-alpha production by IFN-gamma was also suppressed by rMNSF beta. The suppressive effect was partly neutralized by the addition of the serine/threonine phosphatase inhibitor, okadaic acid. This finding suggests that serine/threonine protein phosphatases type 1 and/or 2A may be implicated in the mechanism of action of MNSF.