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 cytokines on the in vitro synthesis of IL-10 by human monocytes and macrophages. In the IL-1 alpha clinical trial, patients received 0.03 g/kg of 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. Thereafter, the levels rapidly declined to baseline within 8 h. The peak plasma IL-10 levels measured on days 3 and 5 of therapy were somewhat less pronounced than those on day 1. IL-2 immunotherapy was also associated with the induction of circulating IL-10. These patients were treated with high-dose (6 x 10(5) IU/kg) IL-2 every 8 h for 5 consecutive days. IL-10 was detectable in these patients within 2-4 h after the first IL-2 infusion (105 +/- 12 pg/mL). In contrast to the transient bursts of IL-10 detected in patients treated with IL-1 alpha, IL-10 levels 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 associated with detectable levels of circulating IL-10. Peripheral blood mononuclear cells and in vitro-derived macrophages synthesized similar amounts of IL-10 after stimulation with IL-1 alpha or IL-2, but were unresponsive to IL-6. These results suggest that the proinflammatory cytokines 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 synthesis.
Tilg
H
H
Department of Medicine, University Hospital Innsbruck, Austria.
Atkins
M B
MB
Dinarello
C A
CA
Mier
J W
JW
D006801:Humans; D007375:Interleukin-1 / Q000627:therapeutic use; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000097:blood; D007376:Interleukin-2 / Q000627:therapeutic use; D015850:Interleukin-6 / Q000627:therapeutic use; D007378:Interleukins / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D009369:Neoplasms / Q000628:therapy*; D010865:Pilot Projects; D011994:Recombinant Proteins / Q000627:therapeutic use
D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D007378:Interleukins; D011994:Recombinant Proteins; D016753:Interleukin-10