Effect of immunosuppressive substance against the potency of natural human tumor necrosis factor as biological response modifier

TNF is a cytokine with the activity of a BRM (biological response modifier). TNF-α and TNF-β enhanced NK activity of peripheral blood mononucleocytes of a normal donor, but not in a cancer patient. ISS, a glocoprotein extracted from the ascitic fluid of a colon cancer patient with immunosuppressive properties, ia also detected in large quantities in the serum of cancer patients. NK activity of a normal donor which was in an immunosuppressive state by the administration of ISS was not affected by treatment of TNF-α or TNF-β, but the suppressed NK activity was improved by the combination of TNF with IFN-α or IFN-γ. On the other hand, NK activity of a cancer patient treated with anti-IS antiserum which was obtained from serum of rabbit immunized by ISS was enhanced by both TNFs. These findings suggest that ISS suppresses the effect of TNFs on NK activity. Furthermore, the effect of TNF as a BRM is inhibited in cancer patients due to the high dose of ISS in the serum, and that the combination of TNF with other cytokines, such as IFN, is more effective than the single use of TNF, clinically.