Induction of immunity and inflammation by interleukin-12 family members.
The interleukin (IL)-12 family is composed of three heterodimeric cytokines, IL-12 (p40p35), IL-23 (p40p19), and IL-27 (EBI3p28), and of monomeric and homodimeric p40. This review focuses on the three heterodimeric members of the IL-12 family. The p40 and p40-like (EBI3) subunits have homology to the IL-6R, the other subunits (p35, p19, and p28) are homologous to each other and to members of the IL-6 superfamily. On the basis of their structural similarity, it was expected that the members of the IL-12 family have overlapping pro-inflammatory and immunoregulatory functions. However, it was surprising that they also show very distinct activities. IL- 12 has a central role as a Th1-inducing and -maintaining cytokine, which is essential in cell-mediated immunity in nonviral infections and in tumor control. IL-23 recently emerged as an end-stage effector cytokine responsible for autoimmune chronic inflammation through induction of IL-17 and direct activation of macrophages. Very recently, IL-27 was found to exert not only a pro-inflammatory Thl-enhancing but also a significant anti-inflammatory function.
Alber
G
G
Institute of Immunology, College of Veterinary Medicine, University of Leipzig, Germany. alber@vetmed.uni-leipzig.de
Al-Robaiy
S
S
Kleinschek
M
M
Knauer
J
J
Krumbholz
P
P
Richter
J
J
Schoeneberger
S
S
Schuetze
N
N
Schulz
S
S
Toepfer
K
K
Voigtlaender
R
R
Lehmann
J
J
Mueller
U
U
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism; D001327:Autoimmune Diseases / Q000276:immunology; D015551:Autoimmunity / Q000502:physiology; D007107:Immune System / Q000502:physiology*; D007249:Inflammation / Q000276:immunology*; D018664:Interleukin-12 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005810:Multigene Family; D009928:Organ Specificity; D018123:Receptors, Interleukin / Q000378:metabolism; D053707:Receptors, Interleukin-12; D015398:Signal Transduction / Q000502:physiology
D000970:Antineoplastic Agents; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D018664:Interleukin-12