The interleukin-12/interleukin-12-receptor system: role in normal and pathologic immune responses

MK Gately, LM Renzetti, J Magram… - Annual review of …, 1998 - annualreviews.org
MK Gately, LM Renzetti, J Magram, AS Stern, L Adorini, U Gubler, DH Presky
Annual review of immunology, 1998annualreviews.org
▪ Abstract 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 β1 and β2. Of these two subunits, β2 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 …
Abstract
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 β1 and β2. Of these two subunits, β2 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.
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