Premium
Osteopontin, a Protein with Cytokine‐like Properties, is Associated with Inflammation in Crohn's Disease
Author(s) -
Agnholt J.,
Kelsen J.,
Schack L.,
Hvas C. L.,
Dahlerup J. F.,
Sørensen E. S.
Publication year - 2007
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2007.01908.x
Subject(s) - osteopontin , tumor necrosis factor alpha , cytokine , medicine , immune system , inflammation , immunology , crohn's disease , t cell , il 2 receptor , interferon gamma , interleukin , endocrinology , disease
In Crohn's disease (CD) mucosal T‐cells produce increased interferon‐ γ (IFN‐ γ ) and tumour necrosis factor‐ α (TNF‐ α ) levels and TNF‐ α 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‐ γ , TNF‐ α , 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‐ γ and TNF‐ α 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.