CHARACTERIZATION OF ANTI-HUMAN INTERLEUKIN-18 (IL-18) INTERFERON-GAMMA-INDUCING FACTOR (IGIF) MONOCLONAL-ANTIBODIES AND THEIR APPLICATION IN THE MEASUREMENT OF HUMAN IL-18 BY ELISA/

Interleukin-18 (IL-18)/interferon-gamma-inducing factor (IGIF) is a no vel cytokine, which is a potent inducer of IFN-gamma production and pl ays an important role in Th1 responses. In order to develop a specific ELISA for the measurement of human IL-18, we established 13 anti-huma n IL-18 monoclonal antibodies and characterized them. 7 murine anti-hu man IL-18 mAbs and 6 rat anti-human IL-18 mAbs were obtained by fusion of splenocytes from mice or rats immunized with human IL-18, with SP2 /0 myeloma cells, These antibodies were classified into 4 groups accor ding to competitive binding ELISAs to the human IL-18 molecule, 1 muri ne mAb and all 6 rat mAbs neutralized IFN-gamma production induced by IL-ls. A specific human IL-18 ELISA was developed using two neutralizi ng mAbs (#125-2B and #159-12B). This ELISA detects human IL-18 with a minimum detection limit of 10 pg/ml, but does not react with heat-dena tured human IL-18. The ELISA does not show any cross-reactivity with o ther cytokines. Using this assay, human IL-18 was measurable in the pl asma of leukemia patients. This ELISA would become a powerful tool for investigating the relationship between IL-18 and various diseases or analyzing the control mechanisms of IL-18 production from IL-18 produc ing cells. (C) 1997 Elsevier Science B.V.