The light and the dark sides of Interleukin-10 in immune-mediated diseases and cancer.

Objectives. In order to enhance the immunity of cancer patients to prevent relapse or to prolong survival time, umbilical cord blood mononuclear cells (UCMCs) were transplanted to cancer patients. Patients and Methods. UCMCs were transfused to 63 immunocompromised gastrointestinal cancer patients with nonmyeloablative (NMA) conditioning regimen. Results. The clinical study showed that the number of both T and B cells increased much more rapidly after transfusion of UCMCs than that of the control group without transplantation (p < 0.01). Proinflammation cytokines IFNγ and TNFα in serum increased to or above the normal range in 80.9% of patients at 12 weeks after UCMC transfusion. However, they recovered to the normal range in 21.7% of patients at the same time point in the control group only. In addition, the clinical investigation also showed that the transfusion of UCMC increased stable disease (SD) and reduced progressive disease (PD) significantly (p < 0.01); however, it did not have significant effects on complete response (CR), partial response (PR), or mortality rates compared with the control group (p > 0.05). Conclusions. UCMCs have powerful repairing effects on damaged cells and tissues and may reconstruct the impaired immunity. Transfusion of UCMCs could reconstruct the immunity of cancer patients with immunosuppression.

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“…This clinical study confirmed that cancer patients have elevated anti-inflammation cytokine after conventional therapies [25, 26]. …”

Section: Discussionsupporting

confidence: 69%

Immunity Enhancement in Immunocompromised Gastrointestinal Cancer Patients with Allogeneic Umbilical Cord Blood Mononuclear Cell Transfusion

Qiu

Zhao

Yun

et al. 2017

BioMed Research International

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“…Interestingly, as compared to patients with OA, there are higher numbers of CCR6 + IL-7R + TH17-cells [18, 19] and CXCR5 + ICOS + Tfh-cells in SF among many but not all patients with RA. Importantly, both subsets can produce IL-10, but provide help to B cells in the production of IgG, and could play a pathogenic role in autoantibody-driven autoimmune disease [22]. …”

Section: Discussionmentioning

confidence: 99%

Differences in serum and synovial CD4+ T cells and cytokine profiles to stratify patients with inflammatory osteoarthritis and rheumatoid arthritis

et al. 2017

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BackgroundThe aim was to investigate CD4+T-cell subsets, immune cells and their cytokine profiles in blood and synovial compartments in rheumatoid arthritis (RA) and inflammatory osteoarthritis (OA) to define specific immune signatures.MethodsPeripheral blood, synovial fluid (SF) and synovial membranes (SM) of RA and OA patients were analyzed. CD4+T-cell subset frequencies were determined by flow cytometry, and cytokine concentrations in serum and SF were measured by ELISA.ResultsIn peripheral blood, OA patients had altered frequencies of regulatory T-cell subsets, and higher frequencies of Th17 and of Th1/17 cells than RA patients. In the synovial compartment of OA patients, conventional Th17 cells were largely excluded, while Th1/17 cells were enriched and more frequent than in RA patients. Conversely, in the synovial compartment of RA patients, regulatory T cells and Tfh cells were enriched and more frequent then in OA patients. IL-17 and Blys were increased both in serum and SF of RA patients, and correlated with autoantibodies and disease activity. Notably, Blys levels were already significantly elevated in RA patients with low disease activity score in 28 joints (DAS28) and without autoantibody positivity.ConclusionsAlthough patients with inflammatory OA have immune activation in the synovial compartment, they display different T-cell subset frequencies and cytokine profiles. Soluble mediators such as Blys might help to discriminate mild clinical forms of RA from inflammatory OA particularly at the onset of the disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1305-1) contains supplementary material, which is available to authorized users.

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“…To fulfil the latter task, our immune system is equipped with regulatory circuits provided by regulatory cells and anti‐inflammatory cytokines. Among these cytokines, interleukin (IL)‐10 is undoubtedly one of the best‐known immune messengers with numerous anti‐inflammatory capacities (recently reviewed in ). For example, IL‐10 downmodulates antigen presentation and T cell activation and inhibits the secretion of many inflammatory cytokines and chemokines .…”

Section: Introductionmentioning

confidence: 99%

IFN‐γ stimulates CpG‐induced IL‐10 production in B cells via p38 and JNK signalling pathways

et al. 2018

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The production of IL-10, a potent immunosuppressive cytokine, must be strictly regulated to ensure a balanced immune response. IFN-γ, a key cytokine in multiple immune processes and pathologies, is known as an inhibitor of IL-10 production by monocytes and macrophages, but also has some regulatory functions. In the present study, we explored the role of IFN-γ on Toll-like receptor (TLR)-induced IL-10 production in murine peritoneal and spleen cells and in human peripheral blood mononuclear cells. IFN-γ inhibited IL-10 production induced by TLR2, TLR3, TLR4 and TLR7/8 agonists, but stimulated IL-10 production when cells were triggered with CpG oligodeoxynucleotides, a specific TLR9 agonist. The stimulatory effect of IFN-γ on TLR9-induced IL-10 was restricted to B cells. In line with the increased IL-10, B cells stimulated with CpG and IFN-γ profoundly inhibited CD4 T cell proliferation. Further research into the mechanisms involved, revealed that the mitogen-activated protein kinases p38 and JNK are essential players in this stimulatory effect, and that the phosphatase MKP1 - an inhibitor of p38 and JNK activity - is downregulated after combined stimulation with IFN-γ and CpG. Our data may represent a novel immunoregulatory role of IFN-γ in B cells after triggering of TLR9, by stimulating IL-10 production.

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The light and the dark sides of Interleukin-10 in immune-mediated diseases and cancer.

Cited by 109 publications

References 105 publications

Immunity Enhancement in Immunocompromised Gastrointestinal Cancer Patients with Allogeneic Umbilical Cord Blood Mononuclear Cell Transfusion

Immunity Enhancement in Immunocompromised Gastrointestinal Cancer Patients with Allogeneic Umbilical Cord Blood Mononuclear Cell Transfusion

Differences in serum and synovial CD4+ T cells and cytokine profiles to stratify patients with inflammatory osteoarthritis and rheumatoid arthritis

IFN‐γ stimulates CpG‐induced IL‐10 production in B cells via p38 and JNK signalling pathways

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