IL-2 induces IL-6 production in human monocytes

• Published in: The Journal of immunology (1950) Vol. 148; no. 3; pp. 795 - 800
• Main Authors: Musso, T, Espinoza-Delgado, I, Pulkki, K, Gusella, GL, Longo, DL, Varesio, L
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 01.02.1992; American Association of Immunologists
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Biological and medical sciences; Cells, Cultured; Cytotoxicity, Immunologic; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression - drug effects; Humans; Immunobiology; In Vitro Techniques; Interferon-gamma - pharmacology; Interleukin-1 - pharmacology; Interleukin-2 - pharmacology; Interleukin-6 - biosynthesis; Interleukin-6 - genetics; Lymphokines, interleukins ( function, expression); Monocytes - metabolism; Regulatory factors and their cellular receptors; RNA, Messenger - genetics; Human; Interleukin 6; Immunostimulation; Interleukin 2; Monocyte; Cytokine; Biosynthesis; Mechanism of action; Biological activity
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.148.3.795

IL-2 is a potent activator of effector and secretory activities of human monocytes. Since monocytes are an important source of IL-6, we investigated whether IL-2 can induce IL-6 production and whether regulatory circuits can modulate this process. We found that stimulation of monocytes with IL-2 induced expression of IL-6 mRNA and bioactivity in a dose-dependent manner. Production of IL-6 in monocytes can be induced by other cytokines such as IL-1 beta. By using mAb alpha-IL-1 beta we showed that IL-2-induced IL-6 production is not mediated by the autocrine stimulation of IL-1 beta elicited by IL-2. IL-6 induction by monocytes is not a common response to activating signals because IFN-gamma did not induce IL-6 expression under conditions in which it elicits tumoricidal activity. In contrast, IFN-gamma could completely abrogate the induction of IL-6 expression by IL-1 beta but did not affect the levels of mRNA and the secretion of IL-2-elicited IL-6. We have previously reported that transforming growth factor-beta inhibits IL-6 production in response to IL-1 beta. Studies on the inhibitory activity of transforming growth factor-beta demonstrated that this cytokine differs from IFN-gamma because it inhibited both IL-1- and IL-2-induced IL-6 expression. These data demonstrate that, in human monocytes, both IL-1 and IL-2 stimulate IL-6 expression by independent mechanisms that can be dissociated by the susceptibility to the inhibitory effect of IFN-gamma. IL-6 production is also down-regulated by TGF-beta, whose inhibitory activity is stimulus-unrelated.