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 prod uced by a murine T cell hybridoma, shows a pleiotropic antigen-nonspec ific suppressive function. Most recently, a cDNA encoding a subunit of MNSF (MNSF beta) has been isolated and characterized. Recombinant for m of MNSF beta (rMNSF beta) inhibits lymphokine functions, as does nat ive MNSF. In this study, we investigated whether rMNSF beta also affec ts macrophage function in terms of LPS-induced TNF-alpha production by a mouse macrophage cell line, J774. rMNSF beta suppressed the TNF-alp ha production in a dose-dependent manner. This suppressive effect was remarkably reduced when rMNSF beta was added after 6h of LPS stimulati on. In addition, enhancement of TNF-alpha production by IFN-gamma was also suppressed by rMNSF beta. The suppressive effect was partly neutr alized by the addition of the serine/threonine phosphatase inhibitor, okadaic acid. This finding suggests that serine/threonine protein phos phatases type 1 and/or 2A may be implicated in the mechanism of action of MNSF.