title: The interleukin-12/interleukin-12-receptor system: role in normal and pathologic immune responses.
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 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.
authors.affiliation: Department of Inflammation/Autoimmune Diseases, Hoffmann-La Roche Inc., Nutley, New Jersey 07110, USA. maurice.gately@roche.com
authors.forename: M K
authors.initials: MK
authors.lastname: Gately
authors.forename: L M
authors.initials: LM
authors.lastname: Renzetti
authors.forename: J
authors.initials: J
authors.lastname: Magram
authors.forename: A S
authors.initials: AS
authors.lastname: Stern
authors.forename: L
authors.initials: L
authors.lastname: Adorini
authors.forename: U
authors.initials: U
authors.lastname: Gubler
authors.forename: D H
authors.initials: DH
authors.lastname: Presky
mesh_terms: 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*
chemical_list: D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D018664:Interleukin-12