The species preference of human and murine tumor necrosis factor-α (TNF-α) was evaluated in human and murine systems for cytotoxic/cytostatic effects and receptor binding in vitro and murine systems for toxicity and antitumor activity in vivo. The in vitro cytotoxic/cytostatic effects of both species TNF-α on human and murine cell lines as well as the receptor binding studies using 125I-labeled recombinant human TNF-α demonstrated homologous species preferences. Species preference of TNF-α was also apparent in toxicity studies with BALB/c nu/nu and CB6F1 mice, and antitumor responses of CB6F1 mice to s.c. Meth A sarcoma implants. Moreover the growth of Meth A sarcoma implanted i.p. was not inhibited by either human or murine TNF-α. These results are discussed in view of the potential for underestimation of the biological potency of TNF-α from heterologous sources.

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