THE INFLUENCE OF RECOMBINANT HUMAN INTERLEUKIN-6 ON BLOOD AND IMMUNE PARAMETERS IN MIDDLE-AGED AND OLD RHESUS-MONKEYS

IL-6 is a 26-kDa protein cytokine with pleiotropic activities in both hematopoietic and immune systems. It is one of the major mediators of the acute phase inflammatory response. Recently it has been demonstrat ed that pharmacological doses of human recombinant IL-6 (rhIL-6) inhib it certain murine tumors as well as stimulate thrombopoiesis in mice, dogs, nonhuman primates, and humans. The purpose of our study was to e valuate the effects and toxicity of rhIL-6 administration in nonhuman primates with particular reference to subject age. We treated 10 femal e monkeys of two age groups (midle-aged and old) with rhIL-6 (15 mug/k g/day) for 28 days. The monkeys were observed to be somewhat lethargic and lost an average of 10% of their body weights. The white blood cel l count rose transiently whereas the levels of hemoglobin and hematocr it fell significantly and remained depressed for the same period. Impo rtantly, platelet count rose and remained elevated for the duration of treatments. Serum alkaline phosphatase levels increase significantly and certain parameters of clinical immune competence were altered by I L-6 treatment. Treatment effects were similar in both age groups, but the changes in immune functions were different between the midle-aged and old monkeys. We observed a pattern in which the middle-aged group had a significant decrease in immune functions as a result of IL-6 adm inistration and recovered to pretreatment level despite continuous tre atment, whereas the old monkeys had a more protracted but less signifi cant decline in these same immune functions during the trial. IL-6 tre atment did not cause severe toxicity in any monkey. The potent stimula tory effect of IL-6 on platelet maturation and its potential antitumor activity provide rationale for future clinical development of this ag ent.