INTERLEUKIN 10

IL10ppt.PNG

Interleukin-10 | IL10

  • Alias: Interleukin-10, Cytokine synthesis inhibitory factor

  • IL-10 is an anti-inflammatory TH2 cytokine that has a critical role in limiting the immune response to pathogens to prevent host damage.

  • Though IL-10 is associated with TH2 response, it appears to be more relevant to TReg cell responses. IL-10 is known to be expressed by many adaptive immune cells including TH2, TH17, TReg, and B cells, as well as innate immune cells including dendritic cells (DC), macrophages, mast cells, natural killer (NK) cells, eosinophils, and neutrophils. As IL-10 in produced in several T helper populations, it is proposed that it provides a feedback loop to limit the effector functions of macrophages and DCs on T cells. Once expressed, IL-10 signals through the IL-10 receptor (IL-10R) to activate STAT3.

  • As IL-10 is a strong inhibitor of inflammation, it has become a viable biomarker for various diseases and conditions as well as a therapeutic molecule for certain conditions. In addition to elevated levels in parasitic infection, high expression levels of IL-10 are also found in retroviral infections inducing immunodeficiency. The immunosuppressive properties of IL-10 suggest a possible clinical use of IL-10 in suppressing rejections of grafts after organ transplantations.

  • IL-10 is capable of inhibiting synthesis of pro-inflammatory cytokines such as IFN-γ, IL-2, IL-3, TNFα and GM-CSF made by cells such as macrophages and regulatory T-cells. It also displays a potent ability to suppress the antigen-presentation capacity of antigen presenting cells. However, it is also stimulatory towards certain T cells and mast cells and stimulates B cell maturation and antibody production.

  • Knockout studies suggested the function of Interleukin-10 / IL-10 as an essential immunoregulator in the intestinal tract.

  • Patients with Crohn's disease react favorably towards treatment with bacteria producing recombinant interleukin-10, showing the importance of interleukin-10 for counteracting excessive immunity in the human body.

  • The anti-inflammatory cytokine IL-10 is capable to induce a resistance of the brain cells to ischemia-evoked damages in in vivo and in vitro models of the ischemic insults in rats.

  • This protective effect in cultured hippocampal cells is developed rapidly after application of IL-10 and strongly associated with the IL-10 elicited elimination of [Ca(2+)]i response to ischemia. Thus, our results provide the evidence that anti-inflammatory cytokine IL-10, in addition to an activation of the canonical signaling pathways, is capable to exert the rapid neuroprotective effects through transcription-independent modulation of ischemia-induced intracellular Ca(2+) responses in the brain cells.  

 

Molecules. 2018 May 31;23(6). pii: E1325. doi: 10.3390/molecules23061325.

Study on the Structure of Ginseng Glycopeptides with Anti-Inflammatory and Analgesic Activity.

Luo H1, Zhu D2, Wang Y3, Chen Y4, Jiang R5,6, Yu P7, Qiu Z8.

Author information

Abstract

Panax ginseng is well known for its medicinal functions. As a class of important compound of ginseng, ginsenoside is widely studied around the world. In addition, ginseng glycopeptides also showed good biological activity, but researches in this field are rarely reported. In this study, ginseng glycopeptides (Gg) were first prepared from Panax ginseng by reflux extracted with 85% ethanol and the following purification with Sephadex G-15 column. Then, the inflammatory pain models induced by carrageenan and the rat pain models induced by Faure Marin were established for research on mechanism of analgesic activities. It is showed that Gg had an obvious inhibiting effect on inflammation and a significant reduction on the Malondialdehyde (MDA) of inflammatory foot tissue. And there were significant differences between moderate to high dose of Gg and model group in Interleukin 1β (IL-1β), Interleukin 2 (IL-2), Interleukin 4 (IL-4), Tumor necrosis factor α (TNF-α) and Histamine. The two models can be preliminarily determined that the analgesic effect of Gg may be peripheral, which mechanism may be related to the dynamic balance between proinflammatory cytokines (TNF-α, IL-1β) and anti-inflammatory cytokines (IL-2, IL-4, and Interleukin 10 (IL-10)). A series of methods were used to study Gg in physical-chemical properties and linking mode of glycoside. The high-resolution mass spectrometry was used for identification of the structure of Gg. Moreover, the structure of 20 major Gg were investigated and identified. The structural analysis of Gg was benefit for the next study on structure-activity relationship.

Interleukin-10 Therapy—Review of a New Approach

 

The therapeutic role of interleukin-10 after spinal cord injury

J Neurotrauma. 2013 Aug 1;30(15):1311-24. doi: 10.1089/neu.2012.2651. Epub 2013 Jul 18.

Thompson CD1, Zurko JC, Hanna BF, Hellenbrand DJ, Hanna A.

1Department of Neurological Surgery, University of Wisconsin , Madison, Wisconsin, USA.

Abstract

Spinal cord injury (SCI) is a devastating condition affecting 270,000 people in the United States. A potential treatment for decreasing the secondary inflammation, excitotoxic damage, and neuronal apoptosis associated with SCI, is the anti-inflammatory cytokine interleukin-10. The best characterized effects of IL-10 are anti-inflammatory-it downregulates pro-inflammatory species interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), tumor necrosis factor-α, interferon-γ, matrix metalloproteinase-9, nitric oxide synthase, myeloperoxidase, and reactive oxygen species. Pro-apoptotic factors cytochrome c, caspase 3, and Bax are downregulated by IL-10, whereas anti-apoptotic factors B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X, B-cell lymphoma-extra large (Bcl-xl) are upregulated by IL-10.

IL-10 also provides trophic support to neurons through the IL-10 receptor. Increased tissue sparing, functional recovery, and neuroprotection are seen with an immediate post-SCI systemic administration of IL-10. Treatment of SCI with IL-10 has been used successfully in combination with Schwann cell and olfactory glial cell grafts, as well as methylprednisolone. Minocycline, tetramethylpyrazine, and hyperbaric oxygen treatment all increase IL-10 levels in a SCI models and result in increased tissue sparing and functional recovery. A chronic systemic administration of IL-10 does not appear to be beneficial to SCI recovery and causes increased susceptibility to septicemia, pneumonia, and peripheral neuropathy. However, a localized upregulation of IL-10 has been shown to be beneficial and can be achieved by herpes simplex virus gene therapy, injection of poliovirus replicons, or surgical placement of a slow-release compound. IL-10 shows promise as a treatment for SCI, although research on local IL-10 delivery timeline and dosage needs to be expanded.