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.
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.
Hunter
C A
CA
Department of Pathobiology, University of Pennsylvania, Philadelphia, USA.
Timans
J
J
Pisacane
P
P
Menon
S
S
Cai
G
G
Walker
W
W
Aste-Amezaga
M
M
Chizzonite
R
R
Bazan
J F
JF
Kastelein
R A
RA
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005260:Female; D007369:Interferon Inducers / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000187:drug effects; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000502:physiology; D053577:Interleukin-1 Receptor Accessory Protein; D020382:Interleukin-18; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D011506:Proteins / Q000502:physiology; D017472:Receptors, Interleukin-1 / Q000502:physiology; D012795:Sialoglycoproteins / Q000502:physiology
D000276:Adjuvants, Immunologic; D016207:Cytokines; C507767:Il1rap protein, mouse; C507764:Il1rn protein, mouse; D007369:Interferon Inducers; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D053577:Interleukin-1 Receptor Accessory Protein; D020382:Interleukin-18; D011506:Proteins; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D007371:Interferon-gamma