Immunoregulatory role of interleukin 10 in patients with inflammatory bowel disease

Schreiber, Stefan; Heinig, Thomas; Thiele, H G; Raedler, Andreas

doi:10.1016/0016-5085(95)90692-4

Cited by 358 publications

(227 citation statements)

References 30 publications

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“…Trials of systemic IL-10 in patients with Crohn's disease have achieved only a modest therapeutic benefit, despite the ability of exogenous IL-10 to inhibit proinflammatory cytokine release by mononuclear cells isolated from Crohn's disease tissue in vitro (39). In this paper, we have demonstrated the therapeutic advantage of adenoviral vectors encoding IL-10 over systemic IL-10 administration in the prevention and treatment of colitis in the IL-10 Ϫ/Ϫ mouse.…”

Section: Discussionmentioning

confidence: 89%

The Prevention and Treatment of Murine Colitis Using Gene Therapy with Adenoviral Vectors Encoding IL-10

Lindsay

Ciesielski

Scheinin

et al. 2001

The Journal of Immunology

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IL-10-deficient (IL-10−/−) mice develop colitis with many similarities to Crohn’s disease. Daily IL-10 injections have a short systemic half-life and are unable to induce complete remission in IL-10−/− mice with established disease. In this paper, we investigate the duration, potency, and immunogenicity of gene therapy using an adenoviral vector encoding murine IL-10 (AdvmuIL-10). A single systemic injection of AdvmuIL-10 was sufficient not only to prevent the onset of colitis for at least 10 wk but also to induce clinical and histological remission in mice with established disease. In addition, AdvmuIL-10 diminished the systemic manifestations of disease, including elevated acute-phase proteins, as well as the local consequences of inflammation such as raised stool IL-1β concentrations. Both IL-10 protein and the effects of secreted IL-10 were detectable for 10 wk after AdvmuIL-10 injection. Furthermore, the immunoregulatory effect of a single AdvmuIL-10 injection was manifest both by a reduction in TNF-α, IFN-γ, and RANTES release from stimulated splenocyte cultures, and also by a change in the proportion of CD45RBhigh/low lymphocytes in the spleen compared with control mice. The delivery of AdvmuIL-10 resulted in a significantly diminished host antiadenoviral response compared with control adenoviral vectors. Thus, gene therapy strategies using adenoviral vectors encoding immunoregulatory and antiinflammatory cytokines may prove to be a potent approach for the treatment of chronic inflammatory disease. Antiinflammatory cytokine expression protects against immune responses directed at gene vectors.

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Section: Discussionmentioning

confidence: 89%

The Prevention and Treatment of Murine Colitis Using Gene Therapy with Adenoviral Vectors Encoding IL-10

Lindsay

Ciesielski

Scheinin

et al. 2001

The Journal of Immunology

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“…To determine the anti-inflammatory activity of probiotic Bifidobacterium strains in the BFM, we firstly investigated the effects of these strains on the production of anti-inflammatory cytokine IL-10 by PBMNC isolated from UC patients in vitro. IL-10 down regulates the TNF-α secretion by macrophages [26] . IL-10 knockout mice develop IBD under conventional conditions, indicating the importance of IL-10 in the control of intestinal inflammation [27] .…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory activity of probiotic Bifidobacterium: Enhancement of IL-10 production in peripheral blood mononuclear cells from ulcerative colitis patients and inhibition of IL-8 secretion in HT-29 cells

Imaoka¹,

Shima²,

Kato³

et al. 2008

WJG

152

100

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AIM:To determine the anti-inflammatory activity of probiotic Bifidobacteria in Bifidobacteria-fermented milk (BFM) which is effective against active ulcerative colitis (UC) and exacerbations of UC, and to explore the immunoregulatory mechanisms. METHODS:Peripheral blood mononuclear cells (PBMNC) from UC patients or HT-29 cells were co-cultured with heat-killed probiotic bacteria or culture supernatant of Bifidobacterium breve strain Yakult (BbrY) or Bifidobacterium bifidum strain Yakult (BbiY) to estimate the amount of IL-10 or IL-8 secreted.RESULTS: Both strains of probiotic Bifidobacteria contained in the BFM induced IL-10 production in PBMNC from UC patients, though BbrY was more effective than BbiY. Conditioned medium (CM) and DNA of both strains inhibited IL-8 secretion in HT-29 cells stimulated with TNF-α, whereas no such effect was observed with heatkilled bacteria. The inhibitory effect of CM derived from BbiY was greater than that of CM derived from BbrY. DNAs of the two strains had a comparable inhibitory activity against the secretion of IL-8. CM of BbiY induced a repression of IL-8 gene expression with a higher expression of IκB-ζ mRNA 4 h after culture of HT-29 cells compared to that in the absence of CM. CONCLUSION:Probiotic Bifidobacterium strains in BFM enhance IL-10 production in PBMNC and inhibit IL-8 secretion in intestinal epithelial cells, suggesting that BFM has anti-inflammatory effects against ulcerative colitis.

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“…IL-10 treatment has shown benefits in models of induced colitis (13)(14)(15) and arthritis (14,16), as well as in models of experimental autoimmune encaphalomyelitis, pancreatitis, diabetes mellitus, and experimental endotoxemia in vivo (17)(18)(19)(20). Moreover, patients suffering from Crohn's disease display clinical improvement following IL-10 treatment (21,22).…”

Section: Interleukin-10 (Il-10)mentioning

confidence: 99%

Interleukin-10 Signaling Blocks Inhibitor of κB Kinase Activity and Nuclear Factor κB DNA Binding

Schottelius¹,

Mayo²,

Sartor³

et al. 1999

Journal of Biological Chemistry

481

324

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The transcription factor nuclear factor B (NF-B) coordinates the activation of numerous genes in response to pathogens and proinflammatory cytokines and is, therefore, pivotal in the development of acute and chronic inflammatory diseases. In its inactive state, NF-B is constitutively present in the cytoplasm as a p50-p65 heterodimer bound to its inhibitory protein IB. Proinflammatory cytokines, such as tumor necrosis factor (TNF), activate NF-B by stimulating the activity of the IB kinases (IKKs) which phosphorylate IB␣ on serine residues 32 and 36, targeting it for rapid degradation by the 26 S proteasome. This enables the release and nuclear translocation of the NF-B complex and activation of gene transcription. Interleukin-10 (IL-10) is a pleiotropic cytokine that controls inflammatory processes by suppressing the production of proinflammatory cytokines which are known to be transcriptionally controlled by NF-B. Conflicting data exists on the effects of IL-10 on TNF-and LPS-induced NF-B activity in human monocytes and the molecular mechanisms involved have not been elucidated. In this study, we show that IL-10 functions to block NF-B activity at two levels: 1) through the suppression of IKK activity and 2) through the inhibition of NF-B DNA binding activity. This is the first evidence of an anti-inflammatory protein inhibiting IKK activity and demonstrates that IKK is a logical target for blocking inflammatory diseases.

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Immunoregulatory role of interleukin 10 in patients with inflammatory bowel disease

Cited by 358 publications

References 30 publications

The Prevention and Treatment of Murine Colitis Using Gene Therapy with Adenoviral Vectors Encoding IL-10

The Prevention and Treatment of Murine Colitis Using Gene Therapy with Adenoviral Vectors Encoding IL-10

Anti-inflammatory activity of probiotic Bifidobacterium: Enhancement of IL-10 production in peripheral blood mononuclear cells from ulcerative colitis patients and inhibition of IL-8 secretion in HT-29 cells

Interleukin-10 Signaling Blocks Inhibitor of κB Kinase Activity and Nuclear Factor κB DNA Binding

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