The interleukin-12/interleukin-12-receptor system: role in normal and pathologic immune responses.
Interleukin-12 (IL-12) is a heterodimeric cytokine that plays a central role in promoting type 1 T helper cell (Th1) responses and, hence, cell-mediated immunity. Its activities are mediated through a high-affinity receptor composed of two subunits, designated beta 1 and beta 2. Of these two subunits, beta 2 is more restricted in its distribution, and regulation of its expression is likely a central mechanism by which IL-12 responsiveness is controlled. Studies with neutralizing anti-IL-12 antibodies and IL-12-deficient mice have suggested that endogenous IL-12 plays an important role in the normal host defense against infection by a variety of intracellular pathogens. However, IL-12 appears also to play a central role in the genesis of some forms of immunopathology. Inhibition of IL-12 synthesis or activity may be beneficial in diseases associated with pathologic Th1 responses, such as multiple sclerosis or Crohn's disease. On the other hand, administration of recombinant IL-12 may have utility in the treatment of diseases associated with pathologic Th2 responses such as allergic disorders and asthma.
Gately
M K
MK
Department of Inflammation/Autoimmune Diseases, Hoffmann-La Roche Inc., Nutley, New Jersey 07110, USA. maurice.gately@roche.com
Renzetti
L M
LM
Magram
J
J
Stern
A S
AS
Adorini
L
L
Gubler
U
U
Presky
D H
DH
D000818:Animals; D006801:Humans; D007111:Immunity, Cellular; D018664:Interleukin-12 / Q000276:immunology*; D018123:Receptors, Interleukin / Q000276:immunology*; D053707:Receptors, Interleukin-12; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D018664:Interleukin-12