Immunoregulatory role of interleukin 10 in patients with inflammatory bowel disease.
OBJECTIVE
Active inflammatory bowel disease (IBD) is associated with increased proinflammatory cytokines. Deficiency of interleukin (IL) 10, a contrainflammatory cytokine, leads to the development of colitis in IL-10 knockout mice. We characterized IL-10 regulation of proinflammatory cytokine (tumor necrosis factor [TNF] alpha and IL-1 beta) expression in IBD in vitro and in vivo.


METHODS
IL-10 regulation of IL-1 beta, TNF-alpha, and IL-1 receptor antagonist expression by peripheral monocytes or isolated lamina propria mononuclear cells (LPMNC), respectively, was studied by enzyme-linked immunosorbent assay (cytokine secretion) and by semiquantitative reverse-transcription polymerase chain reaction.


RESULTS
IL-10 down-regulates IL-1 beta and TNF-alpha secretion as well as messenger RNA levels in IBD peripheral monocytes and LPMNC in a dose-dependent manner. In parallel, IL-1 receptor antagonist secretion is induced, and IL-10 can restore diminished in vitro IL-1 receptor antagonist/IL-1 beta ratios in IBD to normal levels. Equal concentrations of IL-10 are detectable in both normal and IBD intestinal lamina propria biopsy homogenates. After topical IL-10 enema treatment of three steroid therapy-refractory patients with ulcerative colitis, in vitro release of proinflammatory cytokines from IBD peripheral monocytes as well as LPMNC is dramatically down-regulated.


CONCLUSIONS
IL-10 down-regulates the enhanced secretion as well as messenger RNA levels of proinflammatory cytokines by IBD mononuclear phagocytes in vitro. In vivo topical application of IL-10 induces down-regulation of proinflammatory cytokine secretion both systemically and locally.
Schreiber
S
S
Department of Medicine, University of Hamburg, Germany.
Heinig
T
T
Thiele
H G
HG
Raedler
A
A
D000328:Adult; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000494:pharmacology / Q000502:physiology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D012795:Sialoglycoproteins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012333:RNA, Messenger; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10