Production of tumor necrosis factor (TNF) by monocytes from cancer patients and healthy subjects induced by OK-432 in vitro, and its augmentation by human interferon gamma.

A cytostatic factor was induced in the supernatants of human blood monocytes cultured in vitro with OK-432 at 0.01 KE/ml or more. This cytostatic activity was almost completely abolished by anti-human TNF antibody, and so was thought to be that of TNF. Recombinant human gamma interferon (IFN-gamma) alone did not induce TNF as described in other reports, but enhanced the induction of TNF by OK-432 when added to monocytes before or with OK-432. Monocytes of 20 patients with cancer of the digestive tract and 10 healthy donors were tested for ability to produce cytostatic activity. The frequencies of positive responses to OK-432 and the mean cytostatic activities of the two groups were similar. Moreover both groups included high responders whose monocytes produced potent cytostatic activity with OK-432 alone, and also low responders. Interestingly, marked synergistic effects of IFN-gamma and OK-432 were observed with monocytes that did not produce potent cytostatic activity with OK-432 alone. These results suggested that OK-432 may have a stronger immunomodulatory effect clinically when used in combination with IFN-gamma.