Synergistic growth-inhibitory activity of tumour necrosis factor and alpha interferon. Contribution to the monocyte-derived cytostatic activity towards human leukaemia K562 cells.

Monocyte supernatants are cytotoxic towards WEHI 164 clone 13 cells and cytostatic towards K562 cells. The cytotoxic activity towards the clone 13 cells is entirely due to tumour necrosis factor alpha (TNF alpha), since it was completely neutralized by recombinant TNF alpha (rTNF) antiserum, and identical dose-response curves were obtained with supernatants and rTNF alpha. The cytostatic activity towards the K562 cells, however, was only partly due to TNF alpha, since this activity was only partly neutralized by the rTNF alpha antiserum. Moreover, the supernatants were found to be more cytostatic towards K562 cells than rTNF alpha preparations that contained comparable amounts of TNF. Alpha interferon (IFN-alpha) also contributed to cytostasis of the K562 cells, since antibodies against IFN-alpha partially inhibited the cytostatic activity in the supernatants, and further inhibition, although not complete, was obtained in the presence of both IFN-alpha antibodies and rTNF alpha antiserum. Moreover, recombinant IFN-alpha-2c (rIFN-alpha-2c) inhibited the growth of K562 cells, acting synergistically with rTNF alpha. Upon cation exchange chromatography, natural TNF in the monocyte supernatants eluted more broadly than rTNF, and significant amounts of TNF alpha were found in all column fractions containing cytostatic activity.