Characterization of anti-inflammatory factors produced by murine tumor cells in culture.

P-815 mastocytoma cells from DBA/2 mice and a 3-methylcholanthrene-induced fibrosarcoma from C57BL/6 mice produced in culture at least two soluble anti-inflammatory factors that inhibited macrophage accumulation in vivo when the factors were injected sc into syngeneic recipients. One factor was a low-molecular-weight peptide (less than 1,000), as judged by ultrafiltration, failure of extraction by lipid solvents, nonsusceptibility to DNase or RNase, partial inactivation by trypsin, and complete inactivation by carboxypeptidase B. The second anti-inflammatory factor had a molecular weight between 30,000 and 100,000 and was also not extractable with lipid solvents. Production of anti-inflammatory factors by P-815 mastocytoma cells was inhibited by cycloheximide and cell irradiation but not by colchicine pretreatment of the cells, suggesting a relationship to protein synthesis rather than cell growth. Soluble anti-inflammatory factors depressed granulocyte as well as macrophage responses. Anti-inflammatory factors were not found in supernatants from cultures of splenocytes, peritoneal exudate cells, or murine lung fibroblasts.