Inhibition of tumor necrosis factor-mediated lysis by spleen cell-conditioned medium

Abstract

A spleen cell-elaborated factor which inhibits both TNF and natural cytotoxic cell lytic activity has been described. Production of this factor is dependent on prostaglandins, and inhibitory activity is abrogated by protein synthesis inhibitors. Furthermore, it was demonstrated that the factor renders TNF sensitive cells refractory to TNF rather than acting on TNF directly. Here we show that the factor is produced by spleen cells from both BALB/c and C57bl/6 mice and inhibits TNF mediated lysis of various TNF sensitive cells. The inhibitory factor has a molecular weight greater than 30 kDal and is heat labile, suggesting it is a protein. Furthermore, the factor is produced by high density spleen cells (e.g. cells of the myeloid lineage). Although it is not clear which cell type(s) is responsible for the production of this factor, these findings suggest that high density spleen cells, which do not produce TNF, can modulate TNF lytic activity via this factor.