Emerging Role of IL-10 in Hypertrophic Scars

Sun, Ziyong; Feng, Yi; Zou, Ming-Li; Zhao, Bin-Hong; Liu, Siyu; Du, Yong; Yu, Sheng; Yang, Minlie; Wu, Junjie; Yuan, Zheng‐Dong; Lv, Guozhong; Zhang, Jiru; Yuan, Feng‐Lai

doi:10.3389/fmed.2020.00438

Cited by 18 publications

(15 citation statements)

References 55 publications

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“…As presented below, this “complement-sensitized” test system enabled the assessment of the role of complement activation in CS/CRS, also highlighting the possible utility of mini-factor H (mfH) against these conditions. In particular, our data suggest that the latter protein, a truncated, recombinant version of the natural complement inhibitor, factor H (fH) ( 11 – 15 ), may have three independent beneficial actions against CS/CRS; suppression of complement activation and complement-dependent IL-6 production, and, stimulation of IL-10 production, a cytokine with anti-inflammatory properties ( 16 – 19 ).…”

Section: Introductionmentioning

confidence: 99%

Mini-Factor H Modulates Complement-Dependent IL-6 and IL-10 Release in an Immune Cell Culture (PBMC) Model: Potential Benefits Against Cytokine Storm

et al. 2021

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Cytokine storm (CS), an excessive release of proinflammatory cytokines upon overactivation of the innate immune system, came recently to the focus of interest because of its role in the life-threatening consequences of certain immune therapies and viral diseases, including CAR-T cell therapy and Covid-19. Because complement activation with subsequent anaphylatoxin release is in the core of innate immune stimulation, studying the relationship between complement activation and cytokine release in an in vitro CS model holds promise to better understand CS and identify new therapies against it. We used peripheral blood mononuclear cells (PBMCs) cultured in the presence of autologous serum to test the impact of complement activation and inhibition on cytokine release, testing the effects of liposomal amphotericin B (AmBisome), zymosan and bacterial lipopolysaccharide (LPS) as immune activators and heat inactivation of serum, EDTA and mini-factor H (mfH) as complement inhibitors. These activators induced significant rises of complement activation markers C3a, C4a, C5a, Ba, Bb, and sC5b-9 at 45 min of incubation, with or without ~5- to ~2,000-fold rises of IL-1α, IL-1β, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13 and TNFα at 6 and 18 h later. Inhibition of complement activation by the mentioned three methods had differential inhibition, or even stimulation of certain cytokines, among which effects a limited suppressive effect of mfH on IL-6 secretion and significant stimulation of IL-10 implies anti-CS and anti-inflammatory impacts. These findings suggest the utility of the model for in vitro studies on CS, and the potential clinical use of mfH against CS.

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Section: Introductionmentioning

confidence: 99%

Mini-Factor H Modulates Complement-Dependent IL-6 and IL-10 Release in an Immune Cell Culture (PBMC) Model: Potential Benefits Against Cytokine Storm

et al. 2021

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“…After burn injury, neutrophils and macrophages release inflammatory growth factors including IL-1, -2, -6, -8 and others as well as IFN-g and TNF-a [68] . IL-10 has been shown to reduce inflammation by sequestering IL-6 or IL-8 and by reducing inflammatory T-cell cytokine production.…”

Section: Potential Role Of Interleukins In Burn Wound Healingmentioning

confidence: 99%

“…IL-10 has been shown to reduce inflammation by sequestering IL-6 or IL-8 and by reducing inflammatory T-cell cytokine production. Administering Prevascar (Renovo, UK), a recombinant human IL-10 product, intradermally during early wound healing [68] improved scar healing in human patients during phase I/II trials [64] . Other clinical trials with recombinant IL-10 to potentially combat various inflammatory diseases [68] are ongoing.…”

Section: Potential Role Of Interleukins In Burn Wound Healingmentioning

confidence: 99%

“…Administering Prevascar (Renovo, UK), a recombinant human IL-10 product, intradermally during early wound healing [68] improved scar healing in human patients during phase I/II trials [64] . Other clinical trials with recombinant IL-10 to potentially combat various inflammatory diseases [68] are ongoing. However, a phase II clinical trial [69] conducted with IL-10 demonstrated no effectiveness in reducing scar formation in humans of continental African ancestral origin [68,70] .…”

Section: Potential Role Of Interleukins In Burn Wound Healingmentioning

confidence: 99%

“…Other clinical trials with recombinant IL-10 to potentially combat various inflammatory diseases [68] are ongoing. However, a phase II clinical trial [69] conducted with IL-10 demonstrated no effectiveness in reducing scar formation in humans of continental African ancestral origin [68,70] . IL-2 may also contribute to the resolution of inflammation and improve the strength of the healed wound.…”

Section: Potential Role Of Interleukins In Burn Wound Healingmentioning

confidence: 99%

See 2 more Smart Citations

Prevention and management of scarring after thermal injury

Wong¹,

Lin²,

Ding³

et al. 2021

PAR

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Survival from burn injury has improved considerably over the past two decades such that the quality of life of the victim of thermal injuries has become a major concern. Severe proliferative scarring or hypertrophic scarring (HTS) is an all too frequent complication of burn wound healing that severely compromises quality of life for surviving burn victims. Prevention of such scarring in burn patients involves better understanding of the pathophysiology of scar formation, development of newer methods for determining depth of burn injury and earlier and advanced surgical interventions. Many established and evolving novel treatments for HTS in patients after thermal injury exist and include antifibrotic pharmaceuticals and cellular-based therapies as reviewed herein.

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Adipose‐derived stem cells enriched with therapeutic mRNA TGF‐β3 and IL‐10 synergistically promote scar‐less wound healing in preclinical models

Wang,

Chen,

Zhang

et al. 2023

Bioengineering & Transla Med

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Skin wound healing often leads to scar formation, presenting physical and psychological challenges for patients. Advancements in messenger RNA (mRNA) modifications offer a potential solution for pulsatile cytokine delivery to create a favorable wound‐healing microenvironment, thereby preventing cutaneous fibrosis. This study aimed to investigate the effectiveness of human adipose‐derived stem cells (hADSCs) enriched with N1‐methylpseudouridine (m1ψ) modified transforming growth factor‐β3 (TGF‐β3) and interleukin‐10 (IL‐10) mRNA in promoting scar‐free healing in preclinical models. The results demonstrated that the modified mRNA (modRNA)‐loaded hADSCs efficiently and temporarily secreted TGF‐β3 and IL‐10 proteins. In a dorsal injury model, hADSCs loaded with modRNA TGF‐β3 and IL‐10 exhibited multidimensional therapeutic effects, including improved collagen deposition, extracellular matrix organization, and neovascularization. In vitro experiments confirmed the ability of these cells to markedly inhibit the proliferation and migration of keloid fibroblasts, and reverse the myofibroblast phenotype. Finally, collagen degradation mediated by matrix metalloproteinase upregulation was observed in an ex vivo keloid explant culture model. In conclusion, the synergistic effects of the modRNA TGF‐β3, IL‐10, and hADSCs hold promise for establishing a scar‐free wound‐healing microenvironment, representing a robust foundation for the management of wounds in populations susceptible to scar formation.

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Emerging Role of IL-10 in Hypertrophic Scars

Cited by 18 publications

References 55 publications

Mini-Factor H Modulates Complement-Dependent IL-6 and IL-10 Release in an Immune Cell Culture (PBMC) Model: Potential Benefits Against Cytokine Storm

Mini-Factor H Modulates Complement-Dependent IL-6 and IL-10 Release in an Immune Cell Culture (PBMC) Model: Potential Benefits Against Cytokine Storm

Prevention and management of scarring after thermal injury

Adipose‐derived stem cells enriched with therapeutic mRNA TGF‐β3 and IL‐10 synergistically promote scar‐less wound healing in preclinical models

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