Restoration of the healing microenvironment in diabetic wounds with matrix-binding IL-1 receptor antagonist

Tan, Jean; Lash, Blake; Karami, Rezvan; Nayer, Bhavana; Lu, Yang; Piotto, Celeste; Julier, Ziad; Martino, Mikaël M.

doi:10.1038/s42003-021-01913-9

Cited by 33 publications

(46 citation statements)

References 61 publications

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“…Anakinra, a recombinant IL-1R antagonist, was shown to accelerate diabetic wound healing by lowering macrophage and neutrophil infiltration [ 155 ]. In addition, Tan and colleagues reported a diabetic wound closure delay by the IL-1–IL-1R1 axis, which could be overcome by engineered ECM-binding IL-1Ra [ 156 ]. An inhibition of molecules that are overproduced in chronic wounds, and thus further complicate the healing process, is another approach.…”

Section: Modulation Of the Immune System To Improve Wound Healingmentioning

confidence: 99%

Immunology of Acute and Chronic Wound Healing

et al. 2021

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Skin wounds greatly affect the global healthcare system, creating a substantial burden on the economy and society. Moreover, the situation is exacerbated by low healing rates, which in fact are overestimated in reports. Cutaneous wounds are generally classified into acute and chronic. The immune response plays an important role during acute wound healing. The activation of immune cells and factors initiate the inflammatory process, facilitate wound cleansing and promote subsequent tissue healing. However, dysregulation of the immune system during the wound healing process leads to persistent inflammation and delayed healing, which ultimately result in chronic wounds. The microenvironment of a chronic wound is characterized by high quantities of pro-inflammatory macrophages, overexpression of inflammatory mediators such as TNF-α and IL-1β, increased activity of matrix metalloproteinases and abundance of reactive oxygen species. Moreover, chronic wounds are frequently complicated by bacterial biofilms, which perpetuate the inflammatory phase. Continuous inflammation and microbial biofilms make it very difficult for the chronic wounds to heal. In this review, we discuss the role of innate and adaptive immunity in the pathogenesis of acute and chronic wounds. Furthermore, we review the latest immunomodulatory therapeutic strategies, including modifying macrophage phenotype, regulating miRNA expression and targeting pro- and anti-inflammatory factors to improve wound healing.

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Section: Modulation Of the Immune System To Improve Wound Healingmentioning

confidence: 99%

Immunology of Acute and Chronic Wound Healing

et al. 2021

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“…Indeed, whilst IL-1 family cytokines are important in the wound healing process, their dysregulation can contribute to pathological outcomes. IL-1 family members have been found to play roles in such inflammatory override, with an essential role being attributed to IL-1β ( 190 ). It has been shown that non-microbial danger signals resulting from hyperglycaemia and obesity can lead to inflammasome activation and release of IL-1β and IL-18 from a number of different cell types, including monocytes/macrophages, known to be involved in all stages of wound healing ( 191 – 196 ).…”

Section: Il-1 Family Cytokines In the Promotion Of Wound Healingmentioning

confidence: 99%

“…IL-1β then sustains the inflammasome activity of macrophages, creating a positive feedback loop ( 197 ). Moreover, a recent study in diabetic mice showed that beside maintaining an inflammatory macrophage profile, increased levels of IL-1β also result in the persistence of inflammatory cells at the wound site, senescence of fibroblasts and high levels of matrix metalloproteinases ( 190 ), which in turn degrade growth factors and extracellular matrix proteins with an important role in wound healing.…”

Section: Il-1 Family Cytokines In the Promotion Of Wound Healingmentioning

confidence: 99%

“…Murine models showed that topical inhibition of caspase 1, the inflammasome, IL-1β or its signalling through IL-1R1, results in the switch from a sustained pro-inflammatory macrophage stage to an anti-inflammatory macrophage profile, reduced levels of proinflammatory cytokines (IL-1β, TNFα, IL-6, CXCL1), chemokines (the murine homologue of IL-8, MIP-1α), and matrix metalloproteases, but increased the levels of anti-inflammatory cytokines (TGF-β1, IL-4, IL-10), tissue inhibitor of metallopeptidase-1 (TIMP-1) and growth factors (FGF-2, PDGF-BB, VEGF-A), facilitating effective wound healing ( 190 , 197 – 200 ). Treatment with IL-1RA has been also shown to reduce postoperative wound pain due to the reduced inflammatory response ( 200 ).…”

Section: Il-1 Family Cytokines In the Promotion Of Wound Healingmentioning

confidence: 99%

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The Immunological Impact of IL-1 Family Cytokines on the Epidermal Barrier

et al. 2021

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The skin barrier would not function without IL-1 family members, but their physiological role in the immunological aspects of skin barrier function are often overlooked. This review summarises the role of IL-1 family cytokines (IL-1α, IL-1β, IL-1Ra, IL-18, IL-33, IL-36α, IL-36β, IL-36γ, IL-36Ra, IL-37 and IL-38) in the skin. We focus on novel aspects of their interaction with commensals and pathogens, the important impact of proteases on cytokine activity, on healing responses and inflammation limiting mechanisms. We discuss IL-1 family cytokines in the context of IL-4/IL-13 and IL-23/IL-17 axis-driven diseases and highlight consequences of human loss/gain of function mutations in activating or inhibitory pathway molecules. This review highlights recent findings that emphasize the importance of IL-1 family cytokines in both physiological and pathological cutaneous inflammation and emergent translational therapeutics that are helping further elucidate these cytokines.

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“…Interleukin-1 Receptor Antagonist IL-1RA By binding to the interleukin-1 receptor, it inhibits the activation of the intracellular signaling cascade of this proinflammatory cytokine [37].…”

Section: Placental Growth Factormentioning

confidence: 99%

The clinical effectiveness of cryopreserved human amniotic membrane in diabetic foot syndrome

Ustymenko¹,

Nemtinov²,

Bolgarska³

et al. 2021

COT

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Diabetic foot syndrome with long-term unhealed wounds is the most common complication and cause of limb amputation in diabetes. The search for effective therapeutic agents and their inclusion in treatment protocols is a priority due to the increase in the number of cases of this socially significant disease and disability among the working population every year. The aim of the study is to evaluate the effectiveness of cryopreserved human amniotic membrane in the treatment of long-term non-healing wounds of the lower extremities in diabetic foot syndrome. Materials and methods. The pilot clinical study described 4 clinical cases of treatment of patients with diabetes mellitus type I and II (1 woman and 3 men aged 52 to 68 years) with long-term unhealed wounds of the limbs under standard therapy. After previous wound sanation the applications of the cryopreserved human amniotic membrane were performed. Once a week after the application, the dynamics of wound healing was assessed. Blood glucose levels were determined before amniotic membrane treatment and two hours after the procedure. Results. As a results of weekly applications of human amniotic membrane there was a gradual decrease in the area of the wound from the original size and increase the rate of healing. Thus, at the time of the second visit (after 7 days) the reduction in the area of the ulcer from the initial size in patient 1 was 33 %, patient 2 – 25 %, patient 3 – 33 % on the sole and patient 4 – 3 %, and the healing rate – 4.7 %, 3.6 %, 4.7 % and 0.43 % per day, respectively. The use of human amniotic membrane did not affect blood glucose levels when comparing values before application and two hours after the procedure. Regular follow-up visits of patients 3, 6, 9 and 12 months after the start of the study showed no recurrence of ulcers. Conclusions. It has been shown that the use of cryopreserved human amniotic membrane in patients with diabetes mellitus and diabetic foot syndrome with long-term unhealed wounds results in complete healing of ulcers with stable remission during the year of observation.

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Restoration of the healing microenvironment in diabetic wounds with matrix-binding IL-1 receptor antagonist

Cited by 33 publications

References 61 publications

Immunology of Acute and Chronic Wound Healing

Immunology of Acute and Chronic Wound Healing

The Immunological Impact of IL-1 Family Cytokines on the Epidermal Barrier

The clinical effectiveness of cryopreserved human amniotic membrane in diabetic foot syndrome

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