Interleukin-18 and IL-18BP in inflammatory dermatological diseases

Front Immunol. 2023 Jan 18:14:955369. doi: 10.3389/fimmu.2023.955369. eCollection 2023.

Abstract

Interleukin (IL)-18, an interferon-γ inducer, belongs to the IL-1 family of pleiotropic pro-inflammatory factors, and IL-18 binding protein (IL-18BP) is a native antagonist of IL-18 in vivo, regulating its activity. Moreover, IL-18 exerts an influential function in host innate and adaptive immunity, and IL-18BP has elevated levels of interferon-γ in diverse cells, suggesting that IL-18BP is a negative feedback inhibitor of IL-18-mediated immunity. Similar to IL-1β, the IL-18 cytokine is produced as an indolent precursor that requires further processing into an active cytokine by caspase-1 and mediating downstream signaling pathways through MyD88. IL-18 has been implicated to play a role in psoriasis, atopic dermatitis, rosacea, and bullous pemphigoid in human inflammatory skin diseases. Currently, IL-18BP is less explored in treating inflammatory skin diseases, while IL-18BP is being tested in clinical trials for other diseases. Thereby, IL-18BP is a prospective therapeutic target.

Keywords: IL-18; IL-18 binding protein; atopic dermatitis; bullous pemphigoid; inflammatory dermatological disease; psoriasis; rosacea.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dermatitis, Atopic*
  • Humans
  • Intercellular Signaling Peptides and Proteins*
  • Interferon-gamma / metabolism
  • Interleukin-18
  • Protein Binding
  • Psoriasis*

Substances

  • Interferon-gamma
  • Interleukin-18
  • interleukin-18 binding protein
  • Intercellular Signaling Peptides and Proteins

Grants and funding

This study was supported by grants from the National Natural Science Foundation of China (81903226, 22177084 and 82073473), the 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (ZYJC21036), the Clinical Research Innovation Project, West China Hospital, Sichuan University (2019HXCX10) and the Fundamental Research Funds for the Science & Technology department of Sichuan Province (Grant Nos. 2022YFQ0054).