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THE PATHOLOGY OF GPP

THE IL-36 PATHWAY PLAYS A KEY ROLE IN THE PATHOGENESIS OF GPP1

The IL-36 pathway is regulated by the interplay between IL-36 agonists and antagonists to ensure a balanced immune response.2,3 When IL-36 is overexpressed or the IL-36Ra is not functioning properly, excessive inflammation results.4

Dysregulated IL-36 signalling leads to a neutrophilic inflammatory response and the development of sterile pustules, a distinct GPP characteristic5-7

In a study, a recombinant IL-1Ra that broadly inhibits the inflammation mediated by both IL-1α and IL-1β showed efficacy in deficiency of IL-1Ra and Pustular Psoriasis, but incomplete responses suggested it is not the central driver of Generalized Pustular Psoriasis (GPP).8

IL-36 is a member of the IL-1 family of cytokines. Although both IL-1 and IL-36 act as drivers of the autoinflammatory responses involved in GPP, evidence suggests that IL-1 in GPP is not central and probably intervenes in a positive feedback loop induced by IL-36.8

SEE HOW THE IL-36 PATHWAY WORKS

LEARN ABOUT THE PATHOGENESIS OF GPP AND HOW IT DIFFERS FROM PLAQUE PSORIASIS4,9

See how GPP can impact patients' lives10,11

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See how GPP can impact patients
References 
  • 1.
    Johnston A, Xing X, Wolterink L, et al. IL-1 and IL-36 are dominant cytokines in generalized pustular psoriasis. J Allergy Clin Immunol. 2017;140(1):109-120. doi:10.1016/j.jaci.2016.08.056.
  • 2.
    Bassoy EY, Towne JE, Gabay C. Regulation and function of interleukin-36 cytokines. Immunol Rev. 2018;281(1):169-178. doi:10.1111/imr.12610
  • 3.
    Carrier Y, Ma HL, Ramon HE, et al. Inter-regulation of Th17 cytokines and the IL-36 cytokines in vitro and in vivo: implications in psoriasis pathogenesis. J Invest Dermatol. 2011;131(12):2428-2437. doi:10.1038/jid.2011.234
  • 4.
    Furue K, Yamamura K, Tsuji G, et al. Highlighting interleukin-36 signalling in plaque psoriasis and pustular psoriasis. Acta Derm Venereol. 2018;98(1):5-13. doi:10.2340/00015555-2808
  • 5.
    Gabay C, Towne JE. Regulation and function of interleukin-36 cytokines in homeostasis and pathological conditions. J Leukoc Biol. 2015;97(4): 645-652. doi:10.1189/jlb.3RI1014-495R
  • 6.
    Marrakchi S, Guigue P, Renshaw BR, et al. Interleukin-36–receptor antagonist deficiency and generalized pustular psoriasis. N Engl J Med. 2011;365(77):620-628. doi:10.1056/NEJMoa1013068
  • 7.
    Navarini AA, Burden AD, Capon F, et al; for the ERASPEN Network. European consensus statement on phenotypes of pustular psoriasis. J Eur Acad Dermatol Venereol. 2017;31(11):1792-1799. doi:10.1111/jdv.14386
  • 8.
    Iznardo H, Puig L. The interleukin-1 family cytokines in psoriasis: pathogenetic role and therapeutic perspectives. Expert Rev Clin Immunol. 2021;17(2):187-199. doi:10.1080/1744666X.2021.1886081
  • 9.
    Benjegerdes KE, Hyde K, Kivelevitch D, Mansouri B. Pustular psoriasis: pathophysiology and current treatment perspectives. Psoriasis (Auckl). 2016;6:131-144. doi:10.2147/PTT.S98954
  • 10.
    Kharawala S, Golembesky AK, Bohn RL, Esser D. The clinical, humanistic, and economic burden of generalized pustular psoriasis: a structured review. Expert Rev Clin Immunol. 2020;16(3):239-252. doi:10.1080/1744666X.2019.1708193
  • 11.
    Gooderham MJ, Van Voorhees AS, Lebwohl MG. An update on generalized pustular psoriasis. Expert Rev Clin Immunol. 2019;15(9):907-919. doi:10.1080/1744666X.2019.1648209