[Production of interleukin 1 during tumor growth]

The production of IL-1 by splenic mononuclear adherent cells (MAC) from BALB/c mice inoculated with Sarcoma 180 (S180) was examined as a possible mechanism underlying the immunosuppression observed in tumor bearing mice. Two different inducers of IL-1 were used to stimulate MAC. A natural polysaccharide PCj3 (1, 5, 10 micrograms/ml) and a lipopolysaccharide (LPS) of E. coli (1, 5, 10, 20 micrograms/ml). The IL-1 activity was assayed by the capacity of the supernatants of MAC cultures in different dilutions (1/5, 1/10, 1/20) to enhance the mitogenic response of murine thymocytes to phytohemagglutinin (PHA). Both stimulants induced comparable levels of IL-1 in normal and 10 day tumor bearing mice. Normal MAC were able to elaborate IL-1 spontaneously in the presence of 1% FCS: the optimum LPS concentration was 20 micrograms/ml in the 1/5 dilution. With regard to PCj3, the optimum concentration was 5 and 10 micrograms/ml in the 1/5 dilution (p less than 0.001 vs control). The maximum activity of IL-1 for MAC of 10 day tumor bearing mice was given by the concentration of 5 micrograms/ml for both stimulants. When MAC were incubated with LPS, the IL-1 production was dose dependent while PCj3 seemed to have reached a saturation level between 5 and 10 micrograms/ml. The increase in tumor size (day 20-30) was associated with a significant decrease in IL-1 production by MAC in response to both stimulants. Therefore, the immunosuppression associated with the late stages of tumor growth may be due to inhibition of IL-1 production.