THE EFFECTS OF A BIOLOGICAL RESPONSE MODIFIER, OK-432, ON TUMOR-INDUCED ALTERATIONS IN THE HOST METABOLISM

The effects of multicytokine inducer, OK-432, on tumor-induced metabol ic alterations were studied by assessing three key regulatory enzymes of gluconeogenesis, de novo fatty acid synthesis and the triglyceride clearance pathways. Two Klinish Einheit (KE) of OK-432 was subcutaneou sly injected on alternate days, for 10 days, into Fischer 344 rats wit h or without methylcholanthrene-induced sarcoma. At the time of sacrif ice, the tumors accounted for approximately 23% of their total body we ight. The injections of OK-432 did not affect the amount of food intak e in either the tumor bearers or the controls. The tissue lipoprotein lipase activities in the epididymal fat pads of the tumor bearers were significantly decreased compared with the controls (P < 0.01). Phosph oenolpyruvate carboxykinase activity in the liver was significantly in creased (P < 0.01), while malic enzyme activity tended to be decreased in the tumor bearers compared with the controls. However, there were no significant differences in those activities depending on the OK-432 injections, even though OK-432 induced tumor necrosis factor (TNF) an d increased cytotoxic activities in the mesenteric lymph nodes as well as in the spleen. Thus, although the role of monokines in inducing ca ncer cachexia is not yet clearly understood, OK-432 was not able to re vert the tumor-induced metabolic alterations which lead to tissue wast ing and cancer cachexia.