Interleukin-36 in hidradenitis suppurativa: evidence for a distinctive proinflammatory role and a key factor in the development of an inflammatory loop

Hessam, Schapoor; Sand, Michael; Gambichler, Thilo; Skrygan, Marina; Rüddel, I.; Bechara, Falk G.

doi:10.1111/bjd.16019

Cited by 89 publications

(80 citation statements)

References 35 publications

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“…225 IL-36α· IL-36β·, and IL-36γ are elevated in the lesional skin of patients with hidradenitis suppurativa. 226 There is also a role for IL-36 in rheumatoid arthritis. IL-36 is found in the synovium of patients with rheumatoid arthritis and levels correlate with IL-1β and chemokines.…”

Section: Role Of Il-36 In Diseasementioning

confidence: 99%

Overview of the IL‐1 family in innate inflammation and acquired immunity

Dinarello

2017

Immunological Reviews

1,310

1,098

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Summary The interleukin-1 (IL-1) family of cytokines and receptors is unique in immunology because the IL-1 family and Toll-like receptor (TLR) families share similar functions. More than any other cytokine family, the IL-1 family is primarily associated with innate immunity. More than 95% of living organisms use innate immune mechanisms for survival whereas less than 5% depend on T-and B-cell functions. Innate immunity is manifested by inflammation, which can function as a mechanism of host defense but when uncontrolled is detrimental to survival. Each member of the IL-1 receptor and TLR family contains the cytoplasmic Toll-IL-1-Receptor (TIR) domain. The 50 amino acid TIR domains are highly homologous with the Toll protein in Drosophila. The TIR domain is nearly the same and present in each TLR and each IL-1 receptor family. Whereas IL-1 family cytokine members trigger innate inflammation via IL-1 family of receptors, TLRs trigger inflammation via bacteria, microbial products, viruses, nucleic acids, and damage-associated molecular patterns (DAMPs). In fact, IL-1 family member IL-1a and IL-33 also function as DAMPs. Although the inflammatory properties of the IL-1 family dominate in innate immunity, IL-1 family member can play a role in acquired immunity. This overview is a condensed update of the IL-1 family of cytokines and receptors.

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Section: Role Of Il-36 In Diseasementioning

confidence: 99%

Overview of the IL‐1 family in innate inflammation and acquired immunity

Dinarello

2017

Immunological Reviews

1,310

1,098

View full text Add to dashboard Cite

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“…In particular, IL-36, a member of IL-1 superfamily, is involved in the inflammasome activation and pro-inflammatory signaling through the activation of nuclear factor-kB (NF-kB) and mitogen-activated protein kinase (MAPK) [ 71 ]. In serum and lesional HS skin, several studies have proven increased levels of IL-36α, IL-36β, and IL-36γ and decreased antagonist cytokines (IL-36Ra, IL-37, IL-38) [ 72 ]. IL-36 increases dendritic cells activation, neutrophil recruitment, keratinocyte proliferation, and secretion of pro-inflammatory mediators (IL-1ß, TNF-α, IL-6, IL-8) stimulating the production of Th1 cells and Th17 cells and their cytokines (interferon gamma (IFN-γ), IL-17, IL-22, and IL-23) [ 73 ].…”

Section: Resultsmentioning

confidence: 99%

“…IL-36 increases dendritic cells activation, neutrophil recruitment, keratinocyte proliferation, and secretion of pro-inflammatory mediators (IL-1ß, TNF-α, IL-6, IL-8) stimulating the production of Th1 cells and Th17 cells and their cytokines (interferon gamma (IFN-γ), IL-17, IL-22, and IL-23) [ 73 ]. Regarding IL-36 antagonists, IL-37 and IL-38 levels have been significantly higher in perilesional HS skin than in healthy controls [ 72 ]. These cytokines are involved in the negative regulation of the inflammatory response, for example, by suppressing the secretion of the Th17 cells cytokines IL-17 and IL-22 [ 74 , 75 ].…”

Section: Resultsmentioning

confidence: 99%

Cytokine Pathways and Investigational Target Therapies in Hidradenitis Suppurativa

Duca

Morelli

Bennardo

et al. 2020

IJMS

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Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease affecting areas with a high density of apocrine glands and characterized by subcutaneous nodules that may evolve into fistulas with pus secretion. Methods: The aim of this review is to investigate all current knowledge on cytokine regulation in the pathogenesis of HS. A systematic literature research using the words “cytokine”, “interleukin”, “pathway”, and “hidradenitis suppurativa” was performed in PubMed/Medline and Scopus/Embase databases. A search of the clinicaltrials.gov website for interventional recruiting and completed trials including the term “hidradenitis suppurativa” was also performed up to August 2020. We will discuss the pathogenetic role of various cytokines in HS and potential therapeutic targets for this debilitating disease. Results: The pathophysiology underlying this complex condition has not been clearly defined. An upregulation of various cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-1, IL-17, IL-23, and other molecules seems to be related to this inflammatory condition. Various cells, such as lymphocytes T Helper 1 and 17 and keratinocytes seem to be involved in the genesis of this condition. Conclusions: Several future studies and clinical trials are necessary in order to have new knowledge about HS and to properly treat this complex condition.

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“…Recent publications have shown an increased expression of proinflammatory interleukins IL-36 (IL-36a, IL-36β and IL-36γ) and decreased antagonist cytokines (IL-36Ra, IL-37, IL-38) in the lesional and perilesional skin of patients with HS [27].…”

Section: Immunological Pathways In Hidradenitis Suppurativa: Current mentioning

confidence: 99%

“…Pro-inflammatory IL-36 are members of the interleukin-1 (IL-1) superfamily, involved in the inflammasome activation, and inducing pro-inflammatory signaling pathways through the activation of the Nuclear Factor-kB (NF-kB) and Mitogen Activated Protein Kinase (MAPK) [27]. These cytokines may have an important role in the onset and regulation of the inflammatory response, especially in those patients with autoimmune and autoinflammatory diseases, including pustular psoriasis, rheumatoid arthritis, and inflammatory bowel diseases [28][29][30].…”

Section: Immunological Pathways In Hidradenitis Suppurativa: Current mentioning

confidence: 99%

Immunological Pathways in Hidradenitis Suppurativa: Current Concepts and Innovative Therapies

Cubilla¹,

Abdalla²,

Criado³

et al. 2018

CRDOA

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Hidradenitis Suppurativa is a chronic and disabling disease characterized by pustules, nodules, abscesses, and scaring. It affects natural body folds (inguinal, axillary, inframammary), perianal region and genitalia. Several comorbidities are related to this disease, such as: obesity, smoking, acne, folliculitis, and hyperandrogenism. Disorders in keratinization, systemic upregulation of complement (C5a) activation and changes in cutaneous microbiome stimulate the development of autoinflammatory state, promoting the increase of CD4+ T-helper lymphocytes (Th-17 and Th-1). These changes stimulate the expression of toll-like receptors type 2, enabling the NLRP3 inflammasome and triggering of the caspase-dependent inflammatory cascade. Intralesional increase of dendritic cells, macrophage and neutrophil influx stimulate the production of pus, promoting necrosis and apoptosis of inflammatory cells undergoing a special type of cell death program, releasing proinflammatory cytokines (pyroptosis). In addition, patients affected with this condition presents an imbalance of IL-36 proinflammatory cytokines and decreased levels of its antagonist receptor IL-36Ra. Treatment is frustrating and includes the use of broad-spectrum antibiotics, surgical procedures, and oral retinoids. The first and only one biologic therapy approved is a TNF-α inhibitor (Adalimumab); other alternatives are under development, inhibiting IL-17 (Secukinumab, Bimekizumab and CJM112) IL-12 and IL-23 (Ustekinumab); and IL-1 (Anakinra, Canakinumab). Recent articles showed that liraglutide, a glucagon-like-1 pep-tide (GLP-1) agonist, could be used to treat one of the comorbidities associated with HS (insulin resistance). Finally, inhibition of IL-36 and C5a could be an option to treat this recalcitrant and exhausting disease. Highlights: Pathogenesis of HS involves genetic and environmental factors that trigger the innate immune response. Several cytokines participate in the inflammatory response of the skin. HS is chronic and relapsing causing a negative impact on patient´s quality of life, expensive medical approaches, and huge number of comorbidities. New biological drugs, former medical treatments and cutaneous surgical interventions can be combined to better assist of patients suffering of HS.

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Interleukin-36 in hidradenitis suppurativa: evidence for a distinctive proinflammatory role and a key factor in the development of an inflammatory loop

Abstract: Our results showed a possible involvement of IL-36 cytokines in the inflammatory network of HS and a dysbalance between the agonistic and antagonistic cytokines in HS skin.

Cited by 89 publications

References 35 publications

Overview of the IL‐1 family in innate inflammation and acquired immunity

Overview of the IL‐1 family in innate inflammation and acquired immunity

Cytokine Pathways and Investigational Target Therapies in Hidradenitis Suppurativa

Immunological Pathways in Hidradenitis Suppurativa: Current Concepts and Innovative Therapies

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