Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes.
TLDR
The results indicate that IL-10 has important regulatory effects on immunological and inflammatory responses because of its capacity to downregulate class II MHC expression and to inhibit the production of proinflammatory cytokines by monocytes.Abstract:
In the present study we demonstrate that human monocytes activated by lipopolysaccharides (LPS) were able to produce high levels of interleukin 10 (IL-10), previously designated cytokine synthesis inhibitory factor (CSIF), in a dose dependent fashion. IL-10 was detectable 7 h after activation of the monocytes and maximal levels of IL-10 production were observed after 24-48 h. These kinetics indicated that the production of IL-10 by human monocytes was relatively late as compared to the production of IL-1 alpha, IL-1 beta, IL-6, IL-8, tumor necrosis factor alpha (TNF alpha), and granulocyte colony-stimulating factor (G-CSF), which were all secreted at high levels 4-8 h after activation. The production of IL-10 by LPS activated monocytes was, similar to that of IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF), and G-CSF, inhibited by IL-4. Furthermore we demonstrate here that IL-10, added to monocytes, activated by interferon gamma (IFN-gamma), LPS, or combinations of LPS and IFN-gamma at the onset of the cultures, strongly inhibited the production of IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF alpha, GM-CSF, and G-CSF at the transcriptional level. Viral-IL-10, which has similar biological activities on human cells, also inhibited the production of TNF alpha and GM-CSF by monocytes following LPS activation. Activation of monocytes by LPS in the presence of neutralizing anti-IL-10 monoclonal antibodies resulted in the production of higher amounts of cytokines relative to LPS treatment alone, indicating that endogenously produced IL-10 inhibited the production of IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF alpha, GM-CSF, and G-CSF. In addition, IL-10 had autoregulatory effects since it strongly inhibited IL-10 mRNA synthesis in LPS activated monocytes. Furthermore, endogenously produced IL-10 was found to be responsible for the reduction in class II major histocompatibility complex (MHC) expression following activation of monocytes with LPS. Taken together our results indicate that IL-10 has important regulatory effects on immunological and inflammatory responses because of its capacity to downregulate class II MHC expression and to inhibit the production of proinflammatory cytokines by monocytes.read more
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Antiangiogenic Effect of Interleukin-10 in Ischemia-Induced Angiogenesis in Mice Hindlimb
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TL;DR: The antiangiogenic effect of IL-10 associated with the downregulation of VEGF expression is underscored and a role for the inflammatory balance in the modulation of ischemia-induced angiogenesis is suggested.
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TL;DR: A mathematical model incorporating major elements of the acute inflammatory response in C57Bl/6 mice was developed and found that a single model with different initiators including the autonomic system could describe the response to various insults.
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Genetic polymorphisms in sepsis and septic shock: role in prognosis and potential for therapy.
TL;DR: In this article, the authors summarize the evidence for a genetic susceptibility to development of sepsis and death from septic infection, discuss design of clinical genetics studies relevant to the study of complex disorders, and consider the candidate genes likely to be involved in the pathogenesis of septic infections.
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IL-10 Potentiates Differentiation of Human Induced Regulatory T Cells via STAT3 and Foxo1
Peter Hsu,Brigitte Santner-Nanan,Mingjing Hu,Kristen K. Skarratt,Cheng Hiang Lee,Michael Stormon,Melanie Wong,Stephen J. Fuller,Ralph Nanan +8 more
TL;DR: It is shown that the presence of IL-10, in addition to TGF-β, leads to increased expansion of Foxp3+ iTregs with enhanced CTLA-4 expression and suppressive capability, comparable to that of natural Tregs, with potential therapeutic implications for the treatment of immune diseases.
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Role of tumor necrosis factor-alpha and interleukin-10 gene polymorphisms in irritable bowel syndrome.
Patrick P. J. van der Veek,Marlies van den Berg,Yvette E de Kroon,Hein W. Verspaget,Ad A.M. Masclee +4 more
TL;DR: The results support the emerging hypothesis that genetically determined immune activity plays a role in the pathophysiology of IBS.
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