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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Journal ArticleDOI
Human glioma-derived interleukin-10 inhibits antitumor immune responses in vitro.
Makoto Hishii,Taizo Nitta,Hiroshi Ishida,Michimasa Ebato,Akihiro Kurosu,Hideo Yagita,Kiyoshi Sato,Ko Okumura +7 more
TL;DR: Investigation of the physiological roles of glioma-derived interleukin (IL)-10 in Class II expression of monocytes, cytokine secretion from lymphocytes, and T cell proliferation in vitro finds impaired T cell responsiveness cannot be solely explained by gliomas-derived IL-10.
Journal ArticleDOI
Natural killer cell stimulatory factor (NKSF) or interleukin-12 is a key regulator of immune response and inflammation.
Giorgio Trinchieri,Maria Wysocka,Annalisa D'Andrea,Manthrasalam Rengaraju,Miguel Aste-Amezaga,Marek Kubin,Nicholas Valiante,Jihed Chehimi +7 more
TL;DR: The impaired ability of HIV seropositive patients to produce NKSF/IL-12 in response to bacterial stimulation may be a factor contributing to their immune depression, and in vitro, and probably in vivo, IL-12 is required for optimal IFN-gamma production.
Journal ArticleDOI
Interleukin-1 and Tumor Necrosis Factor Antagonists Inhibit the Progression of Inflammatory Cell Infiltration Toward Alveolar Bone in Experimental Periodontitis
TL;DR: It is suggested that the conversion from gingivitis to periodontitis is directly associated with the movement of an inflammatory infiltrate toward alveolar bone, and that this activity is at least partially dependent upon IL-1 and/ or TNF.
Journal ArticleDOI
IL-10, but not IL-4, suppresses infection-stimulated bone resorption in vivo.
Hajime Sasaki,Linda Hou,Anita Belani,Cun-Yu Wang,Toru Uchiyama,Ralph Müller,Philip Stashenko +6 more
TL;DR: It is concluded that IL-10, but not IL-4, is an important endogenous suppressor of infection-stimulated bone resorption in vivo, likely acting via inhibition of IL-1α expression.
Journal ArticleDOI
Attenuation of atherogenesis by systemic and local adenovirus-mediated gene transfer of interleukin-10 in LDLr -/- Mice
Jan H. von der Thüsen,Johan Kuiper,Madelon L. Fekkes,Paula de Vos,Theo J.C. Van Berkel,Erik A.L. Biessen +5 more
TL;DR: It is concluded that a marked inhibition of atherogenesis can be achieved by systemic overexpression of Ad.IL‐10, owing to its metabolic and immunomodulatory effects, and it may represent a valuable addition to the armory of anti‐atherosclerotic therapies.
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