Decreased lamina propria effector cell responsiveness to interleukin-10 in ileal Crohn's disease.
We investigated whether a lack of IL-10 production or responsiveness could be involved in Crohn's disease pathogenesis. Lamina propria mononuclear cells, isolated from the ilea of Crohn's disease patients (n = 16) and controls (n = 13), were activated with anti-CD3 mAb in the presence of CD80 transfectants or LPS +/- IFN-gamma. No evidence for deficient IL-10 production by either T cells or macrophages in Crohn's disease was found. However, the efficacy of rhIL-10 to down-regulate IFN-gamma and especially TNF production in cell cultures from the involved tissues of Crohn's disease patients was poor, and the use of an anti-IL-10R mAb even provided evidence for proinflammatory effects of IL-10. This lack of IL-10 effect possibly results from IL-12 activity. We conclude that IL-10 exhibits poor anti- and even potential proinflammatory effects on ileal Crohn's disease lamina propria. These data might explain the lack of therapeutic efficacy when IL-10 is given to Crohn's disease patients.
Colpaert
Stefaan
S
Laboratory of Experimental Immunology, University Hospital and Katholieke Universiteit Leuven, Leuven, Belgium.
Vanstraelen
Kathleen
K
Liu
Zhanju
Z
Penninckx
Freddy
F
Geboes
Karel
K
Rutgeerts
Paul
P
Ceuppens
Jan
J
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism*; D002478:Cells, Cultured; D003424:Crohn Disease / Q000209:etiology / Q000276:immunology*; D004347:Drug Interactions; D006801:Humans; D007077:Ileal Diseases / Q000209:etiology / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology; D018123:Receptors, Interleukin / Q000378:metabolism; D053701:Receptors, Interleukin-10; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007376:Interleukin-2; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma