INVIVO BIOLOGICAL RESULTS OF THE ASSOCIATION BETWEEN INTERLEUKIN-2 AND INTERLEUKIN-3 IN THE IMMUNOTHERAPY OF CANCER

The concomitant generation of macrophage-mediated suppressive events, as documented by the increase in neopterin and soluble interleukin-2 ( IL-2) receptor (SIL-2R), and the enhanced production of cortisol, woul d represent the most investigated phenomena responsible for the reduce d anticancer efficacy of IL-2 immunotherapy in humans. Based on our pr eliminary experimental studies suggesting a modulatory role of IL-3 on immune and endocrine effects induced by IL-2, a study was performed t o evaluate the influence of IL-3 on biological effects of IL-2 cancer immunotherapy. We have evaluated 12 immunotherapeutic courses with IL- 3 plus IL-2, which were performed in 6 patients with metastatic non-sm all cell lung cancer. The results were compared to those seen in 22 co urses with IL-2 alone, carried out in 12 patients with metastatic non- small cell lung cancer. IL-3 was given intravenously at a daily dose o f 1 mug/kg/b.w. at 6 p.m. for 14 consecutive days, starting 7 days bef ore IL-2. IL-2 was given subcutaneously at a dose of 3 million IU twic e/daily for 5 days/week for 3 weeks. The increase in serum levels of t he specific macrophage marker neopterin, induced by IL-2, was complete ly blocked by IL-3. The IL-2-induced SIL-2R rise was significantly low er during IL-3 plus IL-2 than under IL-2 alone. The increase in cortis ol levels in response to IL-2 was neutralised by IL-3. The increase in lymphocyte, T lymphocyte, natural killer (NK) cell, activated T lymph ocyte and eosinophil mean number was significantly higher during IL-3 plus IL-2 than during IL-2 alone. Episodes of fever, asthenia, anorexi a, vomiting, anaemia and thrombocytopenia were significantly more freq uent in patients receiving IL-2 alone than in those treated with IL-3 and IL-2. This preliminary study would suggest that IL-3 may improve t he tolerability of IL-2 immunotherapy and enhance the biological antit umour properties of IL-2 by neutralising cortisol increase and macroph age-mediated suppressive events, with a following potential amplificat ion of Il-2 anticancer efficacy.