Comparison of the effects of interleukin-1 alpha, interleukin-1 beta and interferon-gamma-inducing factor on the production of interferon-gamma by natural killer

• Published in: European journal of immunology Vol. 27; no. 11; p. 2787
• Main Authors: Hunter, C A, Timans, J, Pisacane, P, Menon, S, Cai, G, Walker, W, Aste-Amezaga, M, Chizzonite, R, Bazan, J F, Kastelein, R A
• Format: Journal Article
• Language: English
• Published: Germany 01.11.1997
• Subjects: Adjuvants, Immunologic - pharmacology; Animals; Cytokines - antagonists & inhibitors; Cytokines - pharmacology; Female; Interferon Inducers - pharmacology; Interferon-gamma - biosynthesis; Interferon-gamma - drug effects; Interleukin 1 Receptor Antagonist Protein; Interleukin-1 - antagonists & inhibitors; Interleukin-1 - pharmacology; Interleukin-1 - physiology; Interleukin-1 Receptor Accessory Protein; Interleukin-18; Killer Cells, Natural - drug effects; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Mice; Mice, Inbred C57BL; Mice, SCID; Proteins - physiology; Receptors, Interleukin-1 - physiology; Sialoglycoproteins - physiology
• ISSN: 0014-2980
• DOI: 10.1002/eji.1830271107

Interferon-gamma inducing factor (IGIF) is a recently identified cytokine which stimulates the production of interferon-gamma (IFN-gamma) by T cells and enhances natural killer (NK) cell cytolytic activity. Protein fold recognition, structure prediction and comparative modeling have revealed that IGIF is a member of the interleukin (IL)-1 cytokine family and has prompted the designation IL-1 gamma. Here we report functional similarities between members of the IL-1 family by comparing the effects of IL-1 alpha, IL-1 beta and IGIF on NK cell production of IFN-gamma. All three IL-1 types enhanced NK cell production of IFN-gamma when induced by IL-2 or IL-12, although at high concentrations (> 10 ng/ml), IGIF was five- to tenfold more potent than IL-1 alpha or IL-1 beta. This effect correlated with enhanced levels of mRNA for IFN-gamma when NK cells were stimulated with IGIF plus IL-12. In contrast to IL-12 and IL-2, the ability of IGIF to stimulate NK cell production of IFN-gamma was not increased by IL-1 alpha or IL-1 beta. The ability of IGIF to enhance IFN-gamma production was independent of the type I and type II IL-1 receptors or the IL-1R accessory protein. Together, these results identify IGIF as a potent stimulator of NK cell production of IFN-gamma and demonstrate that the effect of IGIF on NK cell production of IFN-gamma is similar to that of IL-1 alpha and IL-1 beta but distinct from that of IL-12.