IL-33 promotes Staphylococcus aureus-infected wound healing in mice

Int Immunopharmacol. 2013 Oct;17(2):432-8. doi: 10.1016/j.intimp.2013.07.008. Epub 2013 Jul 25.


Interleukin (IL)-33, a newly identified member of IL-1 family of cytokines, plays a crucial role in polarizing Th2-associated immune responses. Recently growing evidence indicates that IL-33 also represents an important mediator of mucosal healing and epithelial restoration. In this study, we investigated the effect of IL-33 on antimicrobial infection and wound healing using a Staphylococcus aureus-infected incision model in mice. Our findings showed that the expression of IL-33 mRNA and protein was promptly increased in cutaneous wound tissues when challenged by methicillin-resistant S. aureus (MRSA). At the same time, exogenous IL-33 administration profoundly inhibited MRSA colonization and accelerated cutaneous wound repair. IL-33 upregulation promoted the proliferation of neutrophils and CXCR2 expression, which is related to augmented neutrophil trafficking into infectious sites for bactericidal effect. In addition, the beneficial effect of IL-33 is also implicated in enhancement of collagen deposition and the expression of extracellular matrix (ECM)-associated genes such as fibronectin and collagen IIIa, which implies a potential effect of IL-33 on matrix synthesis and reepithelialization during the wound repair process. All together, these findings reveal that IL-33 plays an essential effect in maintenance of cutaneous homeostasis and improvement of infectious wound healing.

Keywords: Bacteria; IL-33; Infection; Neutrophil; Wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Load / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Collagen Type III / metabolism
  • Extracellular Matrix / drug effects
  • Fibronectins / metabolism
  • Interleukin-33
  • Interleukins / administration & dosage
  • Interleukins / genetics
  • Interleukins / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils / immunology*
  • Receptors, Interleukin-8B / metabolism
  • Skin / immunology*
  • Skin / microbiology
  • Skin / pathology
  • Staphylococcal Infections / immunology*
  • Staphylococcal Infections / therapy*
  • Staphylococcus aureus / immunology*
  • Wound Healing* / drug effects
  • Wound Healing* / immunology


  • Collagen Type III
  • Fibronectins
  • Il33 protein, mouse
  • Interleukin-33
  • Interleukins
  • Receptors, Interleukin-8B