IL-1 Superfamily Members and Periodontal Diseases

J Dent Res. 2020 Dec;99(13):1425-1434. doi: 10.1177/0022034520945209. Epub 2020 Aug 6.

Abstract

Periodontitis is a complex, multifactorial chronic disease involving continuous interactions among bacteria, host immune/inflammatory responses, and modifying genetic and environmental factors. More than any other cytokine family, the interleukin (IL)-1 family includes key signaling molecules that trigger and perpetuate periodontal inflammation. Over the years, the IL-1 family expanded to include 11 members of cytokines, some with agonist activity (IL-1α, IL-1β, IL-18, IL-33, IL-36α, IL-36β, and IL-36γ), receptor antagonists (IL-1Ra, IL-36Ra), and 2 anti-inflammatory cytokines (IL-37, IL-38). The IL-1 receptor antagonist (IL-1Ra) has emerged as a pivotal player in the defense against periodontitis. IL-33 primarily induces the production of Th2-associated cytokines but acts as an "alarmin" via stimulation of mast cells. The IL-36 subclass of cytokines may be important in regulating mucosal inflammation and homeostasis. IL-37 suppresses innate and acquired immune responses. IL-38 is the most recent member of the IL-1 superfamily and has anti-inflammatory properties similar to those of IL-37 but through different receptors. However, limited evidence exists regarding the role of IL-37 and IL-38 in periodontitis. Despite the development of IL-1 blocking agents, therapeutic blockade of select IL-1 family members for periodontitis has only been partially investigated in preclinical and clinical research, while the development of IL-37 and IL-38 as novel anti-inflammatory drugs has not been considered adequately. Here, we review the key properties of the IL-1 family members and provide insights into targeting or promoting select cytokines as new therapeutic agents.

Keywords: IL-18; IL-33; cytokines; inflammation; interleukin 1; periodontitis.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adaptive Immunity
  • Cytokines*
  • Humans
  • Inflammation*
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-18
  • Interleukins

Substances

  • Cytokines
  • IL-38 protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-18
  • Interleukins