IL-12, also known as natural killer cell stimulatory factor (NKSF) or cytotoxic lymphocyte maturation factor (CLMF), is a pleiotropic cytokine produced primarily by antigen-presenting cells (monocytes/macrophages, dendritic cells and B lymphocytes). IL-12 has multiple effects on T lymphocytes and natural killer (NK) cells, including the ability to stimulate cytotoxicity, proliferation, cytokine production and Th1 subset development (1, 2). IL-12 is a disulfide-linked, 70 kDa (p70) heterodimeric glycoprotein composed of a unique 35 kDa (p35) subunit and a common 40 kDa (p40) subunit that is also present in IL-23. Monomers of the p40 and p35 subunits by themselves do not have IL-12 activity, but the homodimer of p40 has been shown to bind the IL-12 receptor and is an IL-12 antagonist (3, 4). In cells expressing both p35 and p40 mRNAs, p40 mRNA is expressed to a higher level and free p40 subunits not associated with p35 subunits are secreted together with heterodimeric IL-12 p70 (5). Most of the free p40 subunits secreted by the various human cell lines examined have been found to exist as monomers (1). In the culture supernates of various activated human monocytes where free p40 is present in vast excess over p70, the levels of p70 measured by bioassays are consistent with those measured using a p70-specific immunoassay, suggesting that p40 monomers are not efficient IL-12 antagonists (1, 6). In the mouse system, p40 homodimers are produced in vivo and function as IL-12 antagonists (7). Polymorphisms exist in the mouse IL-12/IL-23 p40 sequence.
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