Interleukin 10 Interleukin-10 (IL-10) is an important anti-inflammatory cytokine (Fiorentino, Zlotnik, Mosmann, Howard, & O’Garra, 1991; Fiorentino, Zlotnik, Vieira, et al., 1991). From: Advances in Cancer Research, 2015 Related terms: View all Topics Role of IL-10 and the IL-10 Receptor in Immune Responses A. Howes, ... A. O'Garra, in Reference Module in Biomedical Sciences, 2014 Conclusions and Unanswered Questions on IL-10 IL-10 is an anti-inflammatory cytokine that maintains the balance of the immune response, allowing the clearance of infection while minimizing damage to the host. IL-10 can also dampen the harmful immune responses elicited in autoimmunity and allergy. The consequence of this activity, however, is that IL-10 can contribute to chronic infection. The importance of IL-10 in this balance is supported by a wealth of evidence gathered from studies in both the human and mouse systems. The immune-stimulatory roles of IL-10 are less well understood but may be a factor in influencing the role of IL-10 in antitumor and/or mucosal immune responses while maintaining the response that limits immunopathology. Further understanding of the sources of IL-10 in various contexts, how IL-10 production is regulated in different cell types, and precisely which cells IL-10 in different immunological settings will greatly enhance our ability to use IL-10 as a potential immune therapy in the future. Introduction to Mechanisms of Allergic Diseases Terufumi Kubo, ... Cezmi A. Akdis, in Middleton's Allergy Essentials, 2017 Interleukin-10 (IL-10) IL-10 plays a role in the control of allergy and asthma. IL-10 inhibits many effector cells and disease processes, and its levels are inversely correlated with disease incidence and severity. IL-10 is synthesized by a wide range of cell types, including B cells, monocytes, DCs, NK cells, and T cells. It inhibits proinflammatory cytokine production and Th1 and Th2 cell activation, which is likely attributable to the effects of IL-10 on APCs and its direct effects on T cell function (Table 1-3). IL-10 levels inversely correlate with the incidence and severity of asthmatic disease in the lung. In addition, the levels of IL-10 inversely correlate with skin-prick test reactivity to allergens. Beekeepers, who undergo multiple bee stings and are naturally tolerant to bee venom allergen have a high IL-10 response. IL-10 and IL-10-producing Treg and Breg cells play essential roles in immune tolerance to allergens. In addition, the roles of Treg and Breg cells and IL-10 have been shown in many autoimmune, organ transplantation, tumor tolerance conditions.6 Interleukin-10 YaoZhong Ding, ... Jonathan Bromberg, in Encyclopedia of Hormones, 2003 V.A Inflammation IL-10 has protective effects in experimental endotoxemia and rescues mice from LPS-induced toxic shock, which is correlated with reduced levels of serum TNFα. IL-10 inhibits the production of TNFα and macrophage inflammatory protein-2 (MIP-2); regulates hemodynamic parameters, leukocyte–endothelial cell interactions, and microvascular permeability; and reduces mortality in experimental endotoxemia. Mice treated with anti-IL-10 from birth or IL-10-deficient mice are more susceptible to endotoxin-induced shock than are normal mice. Human volunteers receiving IL-10 after endotoxin challenge suffer fewer systemic symptoms and less cytokine production. Cytokines in GVHD and GVL Kate A. Markey, ... Geoffrey R. Hill, in Immune Biology of Allogeneic Hematopoietic Stem Cell Transplantation (Second Edition), 2019 Clinical Evidence for Interleukin-10 IL-10 polymorphisms were among the first to be correlated with disease outcome in GVHD [187]. The seminal paper by Lin and colleagues demonstrated a clear and dramatic association of recipient IL-10 genotype with GVHD outcome. Donor IL-10 genotype has also been associated with significantly lower risk of grades III–IV aGVHD [188]. The phenotypic correlation of these polymorphisms does remain uncertain however, i.e., it is not clear whether they lead to gain or loss of IL-10 function. It has been hypothesized that the protection from aGVHD is due to enhanced IL-10 production from APC [184]. INTERLEUKINS | IL-10 T.J. Standiford, J.C. Deng, in Encyclopedia of Respiratory Medicine, 2006 Regulation of Production and Activity IL-10 is produced by a variety of cell types, including CD8+ and CD4+ T cells (e.g., T-helper-2 (Th2) cells, regulatory T cells), γδ-T cells, NK cells, NK T cells, B cells, dendritic cells, eosinophils, mast cells, and monocytic cells (e.g., microglia, monocytes, macrophages). Macrophages are the major source of IL-10, although regulatory T cells are now recognized as an important subpopulation of T cells that release IL-10. Nonleukocyte cell populations, including epithelial cells, keratinocytes, and melanoma cells, also express IL-10. In the lung, human alveolar macrophages (AMs), bronchial epithelial cells, and alveolar epithelial cells have been shown to express IL-10 mRNA and protein. In contrast, murine resident AMs secrete minimal amounts of IL-10, although these cells do express IL-10 receptors. Macrophages produce IL-10 in response to inflammatory or infectious stimuli, including lipopolysaccharide, TNF-α, and catecholamines. High levels of IL-10 are also produced under conditions that induce anergy and tolerance, such as repeated antigen stimulation. In these contexts, IL-10 likely provides negative feedback to dampen the magnitude of immune responses. Interestingly, several viruses, such as EBV, produce IL-10 or IL-10-like molecules (vIL-10). The genomes of other viruses, including members of the herpesvirus family, poxvirus, and primate cytomegaloviruses (CMV), also contain homologs of the IL-10 gene. Many vIL-10 proteins share extensive sequence homology with human IL-10. Viral IL-10 appears to engage the same IL-10 receptor in the host and is capable of producing some of the same biological effects as host-derived IL-10. Given the anti-inflammatory properties of IL-10, vIL-10 likely confers a survival advantage for these viruses by suppressing antiviral host immune responses. Interleukin 10 Receptor Signaling Dror S. Shouval, ... Scott B. Snapper, in Advances in Immunology, 2014 Abstract Interleukin 10 (IL10) is a key anti-inflammatory cytokine that can inhibit proinflammatory responses of both innate and adaptive immune cells. An association between IL10 and intestinal mucosal homeostasis became clear with the discovery that IL10 and IL10 receptor (IL10R)-deficient mice develop spontaneous intestinal inflammation. Similarly, patients with deleterious mutations in IL10, IL10RA, or IL10RB present with severe enterocolitis within the first months of life. Here, we review recent findings on how IL10- and IL10R-dependent signaling modulates innate and adaptive immune responses in the murine gastrointestinal tract, with implications of their role in the prevention of inflammatory bowel disease (IBD). In addition, we discuss the impact of IL10 and IL10R signaling defects in humans and their relationship to very early-onset IBD (VEO-IBD). Spinal Cord Injury Samuel David, ... V. Wee Yong, in Handbook of Clinical Neurology, 2012 Interleukin 10 Interleukin 10 (IL-10) is a potent anti-inflammatory cytokine which reduces inflammation in several disease models. Several reports indicate that IL-10 promotes tissue protection and functional recovery after SCI. Mice lacking IL-10 showed worse functional outcome and greater inflammatory response, apoptosis, tissue loss, and edema after spinal cord compression (Genovese et al., 2009) or excitotoxic injury (Abraham et al., 2004). Furthermore, the increased tissue damage observed in IL-10 null mice, could be reversed with IL-10 administration (Abraham et al., 2004). In addition, a single injection of systemically administered IL-10 improved locomotor recovery and reduced TNF-α expression after spinal cord contusion injury in rats (Bethea et al., 1999). However, in another study, the same group failed to observe any protective effects of IL-10 after a similar type of lesion in different strain of rat (Takami et al., 2002). More animal studies are needed to test various doses, mode of delivery and timing of treatment to establish the role of IL-10 in SCI. Interleukin 10 and its Receptor Vijay P. Khatri, Michael A. Caligiuri, in Encyclopedia of Immunology (Second Edition), 1998 Cellular source of IL-10 IL-10 is produced by several types of cells, including activated T lymphocytes, monocytes, B cells as well as nonhematopoietic sources such as keratinocytes, colon carcinoma and melanoma cells. In humans though TH2 T cell clones are the main source of IL-10, many TH1 clones will also secrete IL-10 following antigen-specific stimulation. In contrast, mIL-10 is produced by the TH2 subset of CD4+ T cells but not by TH1 or CD8+ T cells. In humans both CD4+ and CD8+ T cells secrete IL-10 following stimulation with anti-CD3, although significantly higher levels are produced by CD4+ T cells. Among the CD4+ T cells, CD45RO+ memory cells produce 10-fold higher level of IL-10 than naive T-cells (CD45RA+). Murine Ly-1 B cells as well as Epstein–Barr virus transformed human B cells produce IL-10. Human monocytes are also a major source of IL-10 in response to activation with lipopolysaccharide. Interestingly, kinetics studies reveal that IL-10 is synthesized later than other immunoregulatory cytokines by activated T cells or monocytes. This suggests that IL-10 may play a regulatory role for the later phases of the immune response. The Immune Basis of Allergic Lung Disease Stefanie C.M. Burleson, ... Michael R. Van Scott, in Comparative Biology of the Normal Lung (Second Edition), 2015 IL-10 IL-10, originally described as “cytokine synthesis inhibitor factor,” is produced by TH0, TH1, TH2, Treg, cytotoxic T cells, mast cells, and activated monocytes. IL-10 receptors are located on lymphoid, myeloid, and NK cells. IL-10 decreases TH2 signaling by downregulating MHC class II, B7.1/B7.2 and CD23 expression (Bjorgo et al., 2011; Bopp et al., 2009; Baumer et al., 2007; Heijink and Van Oosterhout, 2006). IL-10 suppresses monocyte and macrophage activity, including release of ROI, and downregulates secretion of pro-inflammatory cytokines such as IL-1β, TNF-α, IL-6, IL-8, and MIP-1α. In TH1 cells, IFN-γ and IL-2 synthesis are inhibited, as is synthesis of IL-4 and IL-5 by TH2 cells. In contrast, IL-10 can promote growth of mast cells, T cells, and B cells. However, even these responses can be bimodal, with inhibition observed at high concentrations of IL-10. IL-10 mRNA and protein are reduced in alveolar macrophages from patients with asthma, although the number of IL-10 expressing T cells and macrophages may be increased. In Brown Norway rats, IL-10 is reported to attenuate late-phase responses and eosinophilia postchallenge. In mice, treatment with IL-10 at the time of sensitization decreases eosinophilia (Chung and Barnes, 1999). Studies involving antibodies against IL-10 and IL-10R, as well as IL-10 knockout, have revealed attenuation of AHR and eosinophilia. This apparent inconsistency in the typical TH1 functioning of IL-10 might be explained by the finding that IL-10 can inhibit IL-13Rα2, a protein responsible for binding and inhibiting IL-13, thereby potentially increasing IL-13 effects. It has been noted that mice lacking both IL-10 and IL-13Rα2 exhibit a more severe manifestation of pulmonary allergic disease than mice deficient in IL-10 or IL-13Rα2 alone (Barnes, 2008). Sepsis Hector R. Wong, ... Cláudio Flauzino de Oliveira, in Pediatric Critical Care (Fourth Edition), 2011 Interleukin-10 Interleukin-10 is the best studied and most well known antiinflammatory cytokine.40,41 As an antiinflammatory cytokine, IL-10 serves to antagonize the proinflammatory effects of other cytokines and can thereby keep inflammation “in check.” IL-10 inhibits expression of cytokines such as TNF-α, IL-1β, and IL-8, and can inhibit expression of adhesion molecules. In addition, IL-10 can “deactivate” monocytes by downregulating the expression of MHC surface molecules. Thus IL-10 has a number of interesting properties that could potentially be leveraged therapeutically to limit excessive inflammation during sepsis. This theoretical consideration must be tempered by the ability of IL-10 to deactivate monocytes and thereby potentially impair the ability to adequately clear infection (i.e., the immune suppression paradigm depicted in Figure 103-1). Indeed, it has been reported that in children with multiple organ dysfunction syndrome, higher plasma IL-10 levels correlate with higher mortality, and higher monocyte mRNA levels of IL-10 correlate with increased length of stay in the ICU.42 Similar observations have been reported in adult patients with septic shock.43