Interleukin 12 is expressed and actively released by Crohn's disease intestinal lamina propria mononuclear cells

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 112; no. 4; p. 1169
• Main Authors: Monteleone, G, Biancone, L, Marasco, R, Morrone, G, Marasco, O, Luzza, F, Pallone, F
• Format: Journal Article
• Language: English
• Published: United States 01.04.1997
• Subjects: Blood Cells - metabolism; Cells, Cultured; Colitis, Ulcerative - metabolism; Colitis, Ulcerative - pathology; Crohn Disease - metabolism; Crohn Disease - pathology; Humans; Interferon-gamma - metabolism; Interleukin-12 - genetics; Interleukin-12 - metabolism; Intestinal Mucosa - metabolism; Intestines - pathology; Monocytes - metabolism; Reference Values; RNA, Messenger - metabolism
• ISSN: 0016-5085; 1528-0012
• DOI: 10.1016/S0016-5085(97)70128-8

Cell-mediated immunity is a feature of Crohn's disease (CD). The heterodimer interleukin (IL)-12, produced by phagocytes, induces T-cell cytokines, primarily interferon (IFN)-gamma. This study examined whether CD lamina propria mononuclear cells (LPMCs) express and release bioactive IL-12. LPMCs were isolated from 13 patients with CD, 9 with ulcerative colitis (UC), and 13 controls. Messenger RNA for p40 and p35 IL-12 subunits was evaluated by reverse-transcription polymerase chain reaction. IL-12 was measured by enzyme-linked immunosorbent assay in LPMC culture supernatants. The INF-gamma-inducing effect of unstimulated LPMC supernatants was evaluated. Messenger RNA for both IL-12 subunits was detected in LPMCs of 11 of 13 patients with CD, 1 of 9 patients with UC, and 1 of 13 controls (P < 0.001). IL-12 was measured (10.5 +/- 2 pg/mL at 24 hours) in unstimulated CD LPMCs and was enhanced by pokeweed mitogen, lipopolysaccharide, and staphylococcal enterotoxin B. No IL-12 was detectable in 8 of 9 patients with UC and 12 of 13 control-unstimulated LPMCs. IL-12 induced by pokeweed mitogen and staphylococcal enterotoxin B in UC was lower than in CD and did not differ from controls. An IFN-gamma-inducing effect was restricted to unstimulated CD LPMC supernatants and was inhibited by an anti-IL-12 antibody in a dose-dependent fashion. IL-12 transcripts are expressed in CD intestinal tissues. CD LPMCs are up-regulated in their capability of releasing bioactive IL-12. Expression and release of bioactive IL-12 seem to differentiate CD from UC.