CLONING OF THE CDNA FOR HUMAN IFN-GAMMA-LNDUCING FACTOR, EXPRESSION IN ESCHERICHIA-COLI, AND STUDIES ON THE BIOLOGIC ACTIVITIES OF THE PROTEIN

We have recently reported that a novel molecule, murine IFN-gamma-indu cing factor (IGIF) produced by mouse liver cells, possesses potent bio logic activities, including the induction of IFN-gamma production by s pleen cells and the enhancement of NK cell cytotoxicity, In this paper , we report on the isolation of human IGIF cDNA clones from normal hum an liver cDNA libraries using murine IGIF cDNA as a probe, The amino a cid sequence deduced from the human cDNA clones indicated a 193-amino acid precursor peptide and revealed 65% homology with that of murine I GIF, The amino acid sequence of IGIF also included an IL-1 signature-l ike sequence, Subsequently, the cloned cDNA was expressed in Escherich ia coli, and preliminary studies on the biologic activities of the rec ombinant protein were performed, The recombinant human IGIF induced IF N-gamma production by mitogen-stimulated PBMC and enhanced NK cell cyt otoxicity, in a manner similar to murine IGIF, In addition, recombinan t human IGIF also augmented granulocyte-macrophage-CSF production and decreased IL-10 production, but had no effect on IL-4 production by Co n A-stimulated PBMC, Based on these pleiotropic effects of IGIF, we pr opose that this novel cytokine be designated as IL-18.