Osteopontin, a protein with cytokine-like properties, is associated with inflammation in Crohn's disease.
In Crohn's disease (CD) mucosal T-cells produce increased interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) levels and TNF-alpha antibody treatment [Infliximab (Ifx)] is effective. Osteopontin (OPN), a glycoprotein stimulating activated T-lymphocytes, may be involved in the disturbed immune-regulation but also in normal immune-homeostasis and mucosal repair, since it is expressed in many tissues and present in human milk. This study investigates plasma-OPN levels in CD patients during Ifx treatment and the in vitro effect of OPN on intestinal T cells. Thirty-seven CD patients received three Ifx doses at week 0, 2 and 6. Blood samples, colonic biopsies and clinical scores were obtained before treatment and at week 8, 26 and 52. In-vivo activated T-cell cultures were established from colonic biopsies in the presence of interleukin (IL)-2 and IL-4. The in vitro effect of OPN stimulation on T-cell IFN-gamma, TNF-alpha, and IL-10 production was measured. Plasma-OPN was increased in active CD (increased CRP-level) compared with quiescent disease (P = 0.02) and declined after three Ifx doses (P = 0.04). It was inversely correlated with in vitro T-cell IL-10 production. OPN increased CD69 and CD25 expression and enhanced T-cell IFN-gamma and TNF-alpha production in a dose-dependent fashion with higher levels in CD than in healthy controls (HC), but induced a concomitant higher IL-10 production in HC than CD. In conclusion, plasma-OPN levels are related to CD inflammation. In vitro, OPN-stimulated IL-10 production increases less in T-cell cultures from CD patients than from HC, indicating that IL-10 deficiency may be involved in the defect immune-regulation in CD, even after OPN stimulation.
Agnholt
J
J
Gastro-Immuno Research Laboratory, Department of Medicine V, Aarhus University Hospital, Aarhus, Denmark. jorge@as.aaa.dk
Kelsen
J
J
Schack
L
L
Hvas
C L
CL
Dahlerup
J F
JF
Sørensen
E S
ES
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002478:Cells, Cultured; D003424:Crohn Disease / Q000276:immunology / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D016207:Cytokines / Q000097:blood / Q000502:physiology*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D000069285:Infliximab; D016753:Interleukin-10 / Q000096:biosynthesis / Q000172:deficiency / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D053495:Osteopontin / Q000097:blood / Q000502:physiology*; D013601:T-Lymphocytes / Q000378:metabolism
D000911:Antibodies, Monoclonal; D016207:Cytokines; D018836:Inflammation Mediators; D053495:Osteopontin; D016753:Interleukin-10; D000069285:Infliximab