INDUCTION OF CIRCULATING INTERLEUKIN-10 BY INTERLEUKIN-1 AND INTERLEUKIN-2, BUT NOT INTERLEUKIN-6 IMMUNOTHERAPY

The objective of this study was to investigate the in vivo production of interleukin 10 (IL-10) in cancer patients undergoing immunotherapy with IL-1 alpha, IL-2 or IL-6 and to study the effect of the same cyto kines on the in vitro synthesis of IL-10 by human monocytes and macrop hages, In the IL-1 alpha clinical trial, patients received 0.03 g/kg o f IL-1 alpha as a 30 minute infusion daily for 5 consecutive days. In these patients, plasma IL-10 levels rose rapidly and peaked within 1 h (121 +/- 16 pg/mL; n = 4) after the first IL-1 alpha infusion. Therea fter, the levels rapidly declined to baseline within 8 h. The peak pla sma IL-10 levels measured on days 3 and 5 of therapy were somewhat les s pronounced than those on day 1, IL-2 immunotherapy was also associat ed with the induction of circulating IL-10. These patients were treate d with high-dose (6 x 10(5) IU/kg) IL-2 every 8 h for 5 consecutive da ys, IL-10 was detectable in these patients within 2-4 h after the firs t IL-2 infusion (10(5) +/- 12 pg/mL), In contrast to the transient bur sts of IL-10 detected in patients treated with IL-1 alpha, IL-10 level s progressively increased throughout the treatment course in the IL-2- treated patients reaching peak levels on day 5 (240 +/- 22 pg/mL; n = 10), IL-6 immunotherapy with a 5-day continuous infusion was not assoc iated with detectable levels of circulating IL-10. Peripheral blood mo nonuclear cells and in vitro-derived macrophages synthesized similar a mounts of IL-10 after stimulation with IL-1 alpha or IL-2, but were un responsive to IL-6. These results suggest that the proinflammatory cyt okines IL-1 alpha and IL-2 induce the anti-inflammatory cytokine IL-10 in vitro and in vivo, whereas IL-6 is not able to stimulate IL-10 syn thesis. (C) 1995 Academic Press Limited.