Interleukin-10 paradox: A potent immunoregulatory cytokine that has been difficult to harness for immunotherapy

Abstract

Interleukin-10 (IL-10) is arguably the most potent anti-inflammatory cytokine. It is produced by almost all the innate and adaptive immune cells. These cells also serve as its targets, indicating that IL-10 secretion and action is highly regulated and perhaps compartmentalized. Consistent with this notion, various efforts directed at systemic administration of IL-10 to modulate autoimmune diseases (type 1 diabetes, multiple sclerosis, rheumatoid arthritis, psoriasis) have produced conflicting and largely inconsequential effects. On the other hand, IL-10 can promote humoral immune responses, enhancing class II expression on B cells and inducing immunoglobulin (Ig) production. Consequently, the high IL-10 level in systemic lupus erythematosus (SLE) patients is considered pathogenic and its blockade ameliorates the disease. In this perspective, we review preclinical findings and results of recent clinical studies using exogenous IL-10 to treat the aforementioned autoimmune diseases. In addition, given the limited success of IL-10 supplementation, we suggest that future studies should be expanded beyond modulating the delivery modes to include developing new strategies to protect and replenish the endogenous sources of IL-10. As an example, we provide evidence that aberrant Fas-mediated deletion of IL-10-producing B cells subverts the immunoregulatory role of IL-10 in autoimmune diabetes and that modulation of the Fas pathway preserves the IL-10-producing B cells and completely protects NOD mice from developing the disease.

Association of –1082A>G Polymorphism in the Interleukin-10 Gene with Estimated Glomerular Filtration Rate in Type 2 Diabetes

“…These pathological changes, in turn, lead to renal failure and ESRD. Considering that the main function of IL-10 is to control inflammation [8,9,34], this scenario seems to be a paradox, as the low expression of IL-10 would be expected to be detrimental to renal function due to the loss of anti-inflammatory protection.…”

“…Depending on the circumstances and the cell type, IL-10 may exert immunostimulatory effects by upregulating MHC class II expression on B lymphocytes. IL-10 is expressed by most immune cells, but is not restricted to them [8,9]. Chen et al [6].…”

Identification of periplakin as a major regulator of lung injury and repair in mice

“…Elevated IL-10 expression persisted after bleomycin injury in Ppl -/-mice. IL-10 is an immunosuppressive cytokine that inhibits the production of many proinflammatory cytokines (36). IL-10 also has antifibrotic functions, as it reduces the production and activation of TGF-β in the lung (37,38).…”

Wpływ wybranych cytokin na uszkodzenie narządów w toczniu rumieniowatym układowym

“…: hamowanie wytwarzania cytokin przez limfocyty Th1, hamowanie wytwarzania pobudzonych limfocytów Th1, hamowanie wytwarzania przez makrofagi i monocyty cytokin oraz reaktywnych form tlenu. Blokowanie IL-10 dało pozytywne efekty w leczeniu TRU [46]. Badania wykazały, że stężenie IL-10 u chorych na TRU jest znacznie podwyższone w porównaniu z populacją ogólną i koreluje ze stopniem aktywności choroby (SLEDAI) [47] oraz z produkcją autoprzeciwciał [48].…”