Competitive inhibition of IL12 function by murine IL12p402

The p40 chain of IL-12 (human and mouse), when synthesized in the absence of p35 (e.g. in cells trans-fected with p40 cDNA) or when produced in excess over p35, can be secreted as a monomer, IL-12p40, and as a disulfide linked homodimer, IL-12(p40)2. Murine IL-12(p40)2 because of its high affinity binding to the murine IL-12R (Table 1) is an efficient inhibitor of IL-12 activities both in vitro and in vivo. Synergistic inhibition was observed in combination with certain lL-12-specific antibodies. There are indications that murine IL-12(p40)2 may be synthesized as a physiological inhibitor of IL-12. Human IL-12(p40), is a much poorer competitor for human 11-12 (Table 1); possibly it could be used in combination with suitable antibodies for more efficient inhibition of IL-12 functions.

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