An interleukin 12-related cytokine is up-regulated in ulcerative colitis but not in Crohn's disease

Background & Aims: interleukin 12 (IL-12) is a heterodimeric, macrophage-derived cytokine that is elevated in Crohn's disease (CD). Epstein-Barr virus-induced gene 3 (EBI3) is a recently characterized human glycoprotein that is homologous to the 40-kilodalton chain of IL-12 and forms a heterodimer with the 35-kilodalton chain of IL-12. We investigated the expression of EBI3 in colonic mucosa of normal control subjects, patients with ulcerative colitis (UC), and patients with CD. Methods: Colonic tissue was analyzed for messenger RNA (mRNA) expression by quantitative polymerase chain reaction and for protein expression by immunohistology and Western blotting. Results: EBI3 mRNA was present in intestinal biopsy specimens from healthy subjects and patients with CD but was elevated only in active UC. EBI3 levels in UC specimens correlated with histological scores of activity and T-cell infiltration. EBI3-positive cells that had a shape consistent with that of macrophages were identified in the lamina propria, and protein was detected by Western blotting. Conclusions: EBI3 is a novel IL-12-related cytokine that is expressed by macrophage-like cells in normal intestine and CD and has enhanced expression in active UC but not in active CD.