IL-6/IFN-beta-2 as a circulating hormone. Induction by cytokine administration in humans

• Published in: The Journal of immunology (1950) Vol. 142; no. 5; pp. 1542 - 1547
• Main Authors: Jablons, DM, Mule, JJ, McIntosh, JK, Sehgal, PB, May, LT, Huang, CM, Rosenberg, SA, Lotze, MT
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01-03-1989
• Subjects: C-Reactive Protein - biosynthesis; C-Reactive Protein - blood; Chromatography, Affinity; Glucose-6-Phosphate Isomerase - biosynthesis; Glucose-6-Phosphate Isomerase - blood; Humans; Hydrocortisone - biosynthesis; Hydrocortisone - blood; Injections, Intravenous; Interleukin-6; Interleukins - biosynthesis; Interleukins - blood; Interleukins - isolation & purification; Molecular Weight; Neoplasms - blood; Recombinant Proteins - administration & dosage; Recombinant Proteins - blood; Tumor Necrosis Factor-alpha - administration & dosage; Tumor Necrosis Factor-alpha - blood
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.142.5.1542

IL-6/IFN-beta 2 is a family of phosphoglycoproteins ranging in size from 19 to 30 kDa which elicits a broad range of physiologic and immune responses. Several cytokines, including TNF, have been shown to stimulate IL-6 production in cell culture. In this report, we describe the rapid induction of circulating biologically active IL-6 by the systemic administration of rTNF to patients with cancer. Low levels of IL-6 activity could be detected in the sera of patients as early as 5 min after rTNF infusion. IL-6 levels peaked approximately 2 to 3 h after rTNF bolus administration and were undetectable in most cases within 8 h. IL-6 was detected in two separate bioassays--the hybridoma B9 proliferation and the hepatocyte-stimulating factor assay. Maximum detectable levels of IL-6 ranged from 160 to 310 hybridoma growth factor units and 11-82 ng/ml in the hepatocyte-stimulating factor assay. IL-6 induction decreased after serial, daily doses of rTNF. Serial serum samples of patients receiving IL-2 or IFN-alpha were also assayed for IL-6 production. IL-2-treated but not IFN-alpha-treated patients generated low levels of IL-6 (range less than 20 to 95 hybridoma growth factor units/ml). Interestingly, in patients treated with IL-2, serum levels of TNF were detectable and peak TNF activity preceded measurable IL-6 levels. Serum levels of acute phase plasma proteins and of corticosteroid rose in response to rTNF administration. C-reactive protein increased (2.5 to 4.0-fold) within 8 h of rTNF administration and cortisol levels rose (10- to 20-fold) within 4 h after rTNF injection. We conclude that rTNF administration in man leads to the induction of circulating IL-6 which, due to its broad range of activities, may be an important physiologic signal regulating the immune response.