Induction of endogenous cytokine-mRNA in circulating peripheral blood mononuclear cells by IL-2 administration to cancer patients.
The lymphokine IL-2 plays a central role in immune regulation. Recent clinical trials have shown that when administered systemically either alone, or in combination with lymphokine-activated killer cells, IL-2 can cause regression of metastatic tumors in some patients with a variety of otherwise refractory cancers. To evaluate the mechanism of in vivo action of IL-2, as well as the toxicity associated with its administration, we have studied the in vivo cytokine-mRNA expression of circulating PBMC in cancer patients undergoing treatment with high dose IL-2. Before IL-2 administration, we found low level or no evidence of cytokine-mRNA expression in PBMC. After IL-2 infusion, circulating PBMC showed enhanced proliferative activity and contained significant levels of mRNA for TNF-alpha and IL-6 as well as mRNA for the p55 IL-2R, Tac, but no mRNA coding for granulocyte-monocyte-CSF and TNF-beta (lymphotoxin). IL-1 beta mRNA was expressed at very low levels in circulating PBMC after IL-2 infusion. Each of these cytokine -mRNA was, however, inducible in vitro by stimulation of PBMC with IL-2 alone. The results of these in vivo studies suggest that IL-2 may be a physiologic inducer of TNF and IL-6 which, because of their pleiotropic effects, may be important endogenous signals in the body's immune response and account for some of the physiologic changes seen in patients receiving high dose IL-2.
Kasid
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Surgery Branch, National Cancer Institute, Bethesda, Maryland 20892.
Director
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Rosenberg
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D001685:Biological Factors / Q000378:metabolism*; D016207:Cytokines; D004334:Drug Administration Schedule; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000097:blood; D015850:Interleukin-6; D007378:Interleukins / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000302:isolation & purification; D015375:Receptors, Interleukin-2 / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D001685:Biological Factors; D016207:Cytokines; D007376:Interleukin-2; D015850:Interleukin-6; D007378:Interleukins; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha