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

G Monteleone, L Biancone, R Marasco, G Morrone… - Gastroenterology, 1997 - Elsevier
G Monteleone, L Biancone, R Marasco, G Morrone, O Marasco, F Luzza, F Pallone
Gastroenterology, 1997Elsevier
BACKGROUND & AIMS: 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. METHODS: 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 …
BACKGROUND & AIMS
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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. (Gastroenterology 1997 Apr;112(4):1169-78)
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