Cloning of a cDNA encoding bovine Interleukin-18 and analysis of IL-18 expression in macrophages and its IFN-gamma-inducing activity

Interleukin-18 (IL-18) is a recently described cytokine that enhances inter feron-gamma (IFN-gamma) production, either independently or synergistically with IL-12, These properties identify IL-18 as an immunoregulatory cytokin e that may be pivotal in host defense against intracellular pathogens. We h ave isolated and sequenced a cDNA encoding bovine IL-18, The open reading f rame (ORF) is 582 bp in length, encoding a predicted 192 amino acid (aa) pr ecursor protein. Multiple sequence alignment demonstrated that bovine IL-18 has 65% and 78% identity with the predicted amino acid sequences of murine and human IL-18, respectively. IL-18 mRNA was constitutively present in bo vine peripheral blood monocyte-derived macrophages (MDM), with no upregulat ion on stimulation with lipopolysaccharide (LPS), IL-18 transcripts were we akly detected in B Lymphocytes but inducible in the B cell line BL-3, Human recombinant IL-18 (rHuIL-18) induced IFN-gamma production by PHA-stimulate d peripheral blood mononuclear cells (PBMC), which was potentiated by rHuIL -12. Further, rHuIL-12 and rHuIL-18 enhanced proliferation of untreated PBM C, Antigen-specific T cell lines demonstrated IL-18-dependent enhancement o f IFN-gamma production, indicating that bovine T cells are one of the leuko cyte subsets that respond to IL-18, Analysis of IL-18 expression and its ab ility to induce IFN-gamma production by bovine lymphocytes are important co nsiderations for understanding mechanisms of protective immunity and design ing vaccines for intracellular pathogens.