Interleukin-10 Therapy—Review of a New Approach

Asadullah, Khusru; Sterry, Wolfram; Volk, Hans‐Dieter

doi:10.1124/pr.55.2.4

Cited by 821 publications

(652 citation statements)

References 309 publications

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“…Our observations made in splenocytes of untreated rats show that CB-01-05 interferes with cytokines profile, reducing the production of IFN-c and increasing the expression of TNF-a, IL-2, and IL-10. The combined reduction of IFN-c and the increase of IL-10 could account for the observed anti-inflammatory activity of CB-01-05, considering the pivotal role of IFN-c in impairing intestinal healing [23], and the well-known immunoregulatory function of IL-10 [24]. CB-01-05 also shows a profile of activity different from that of UFH, resulting more effective as an inhibitor of IFN-c production, but consistently less potent in eliciting the release of TNF-a and, in particular, IL-2.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Intracolonic Administration of Low-Molecular-Weight Heparin CB-01-05, Compared to Other Low-Molecular-Weight Heparins and Unfractionated Heparin, in Experimentally Induced Colitis in Rat

et al. 2008

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Purpose Parenteral administration of lowmolecular-weight heparins (LMWHs) and unfractionated heparin (UFH) resulted effective in improving the symptoms of experimental colitis in rat. Today, there is little information about their activity by intracolonic instillation. The scope of this study was to evaluate the ability of CB-01-05 (a LMWH with a mean molecular weight of about 5,700), compared to a series of other LMWHs and to UFH, directly instilled into the distal colon of the rat, to ameliorate dinitrobenzene (DNB)-induced experimental colitis. Method Adult male Wistar rats underwent colitis induction by intracolonic instillation of DNB. Starting 24 h after colitis induction, CB-01-05 (0.005-0.9 mg), other LMWHs (0.3-0.6 mg), and UFH (0.6 mg) were instilled, by rectal route, into the distal colon once a day for three consecutive days. On the day following the last administration, the animals were sacrificed and the distal colon was isolated, weighed, macroscopically examined, and processed for histology. Additional experiments in rat splenocytes, performed in order to elucidate the anti-inflammatory mechanisms of CB-01-05, were performed. Results Among the tested items, only CB-01-05 at doses ranging from 0.2 to 0.9 mg was significantly effective in reducing colon weight increase and in improving both the mucosal damaged area and the histological score. The other LMWHs resulted far less effective, showing decreasing activity closely related with the decrease of their molecular weight, thus demonstrating their biological nonequivalence. CB-01-05 resulted also more active than UFH. CB-01-05 was shown to interfere with cytokines production by rat splenocytes, mainly inhibiting interferon (IFN)-c expression. Conclusions CB-01-05 instilled into the colon is well tolerated, has strong anti-inflammatory effect on DNBinduced colitis in rat, and is the most effective agent among other LMWHs and UFH. These results suggest that the anti-inflammatory activity of CB-01-05, together with its topical administration, could represent a new approach in the management of ulcerative colitis.

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Section: Discussionmentioning

confidence: 99%

Efficacy of Intracolonic Administration of Low-Molecular-Weight Heparin CB-01-05, Compared to Other Low-Molecular-Weight Heparins and Unfractionated Heparin, in Experimentally Induced Colitis in Rat

et al. 2008

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“…The anti-inflammatory effects of IL-10 are mediated by multiple mechanisms involving both the innate and adaptive arms of the immune system. In innate cells, these mechanisms include downregulation of proinflammatory cytokine production [58] and decreased expression of MHC-II and co-stimulatory molecules [59] resulting in decreased T cell activation. B10 cells negatively regulate the ability of dendritic cells to present Ag [60].…”

Section: B10 Cell Regulatory Effectsmentioning

confidence: 99%

“…B10 cells negatively regulate the ability of dendritic cells to present Ag [60]. In CD4 + T cells, IL-10 suppresses T H1 [50] and enhances T H2 polarization [41,59]. B10 cells suppress IFNγ and TNFα responses in vitro [60] and INFγ responses in vivo [36] by Ag-specific CD4 + T cells.…”

Section: B10 Cell Regulatory Effectsmentioning

confidence: 99%

IL-10-producing regulatory B cells (B10 cells) in autoimmune disease

2013

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B cell abnormalities contribute to the development and progress of autoimmune disease. Traditionally, the role of B cells in autoimmune disease was thought to be predominantly limited to the production of autoantibodies. Nevertheless, in addition to autoantibody production, B cells have other functions potentially relevant to autoimmunity. Such functions include antigen presentation to and activation of T cells, expression of co-stimulatory molecules and cytokine production. Recently, the ability of B cells to negatively regulate cellular immune responses and inflammation has been described and the concept of regulatory B cells has emerged. A variety of cytokines produced by regulatory B cell subsets have been reported, with IL-10 being the most studied. In this review, this specific IL-10-producing subset of regulatory B cells has been labeled B10 cells to highlight that the regulatory function of these rare B cells is mediated by IL-10, and to distinguish them from other B cell subsets that regulate immune responses through different mechanisms. B10 cells are a functionally defined subset currently identified only by their competency to produce and secrete IL-10 following appropriate stimulation. Although B10 cells share surface markers with other previously defined B cell subsets, currently there is no cell surface or intracellular phenotypic marker or set of markers unique to B10 cells. The recent discovery of an effective way to expand B10 cells ex vivo opens new horizons in the potential therapeutic applications of this rare B cell subset. This review highlights the current knowledge on B10 cells and discusses their potential as novel therapeutic agents in autoimmunity.

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“…The extraction and testing of ancient DNA was performed under recommended conditions (4). The B27 sequence-specific primers have been described previously (5). Negative control procedures were conducted for all extractions and all PCRs, and, as expected, showed no positive results.…”

Section: Molecular Evidence Of Hla-b27 In a Historical Case Of Ankylomentioning

confidence: 81%

Deficient expression of interleukin‐10 receptor α chain in rheumatoid arthritis synovium: Limitation of animal models of inflammation

Neidhart

Jüngel

Ospelt

et al. 2005

Arthritis & Rheumatism

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Interleukin-10 Therapy—Review of a New Approach

Cited by 821 publications

References 309 publications

Efficacy of Intracolonic Administration of Low-Molecular-Weight Heparin CB-01-05, Compared to Other Low-Molecular-Weight Heparins and Unfractionated Heparin, in Experimentally Induced Colitis in Rat

Efficacy of Intracolonic Administration of Low-Molecular-Weight Heparin CB-01-05, Compared to Other Low-Molecular-Weight Heparins and Unfractionated Heparin, in Experimentally Induced Colitis in Rat

IL-10-producing regulatory B cells (B10 cells) in autoimmune disease

Deficient expression of interleukin‐10 receptor α chain in rheumatoid arthritis synovium: Limitation of animal models of inflammation

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