Attenuated Airway Eosinophilic Inflammations in IL-38 Knockout Mouse Model

Kurume Med J. 2019 May 16;65(2):37-46. doi: 10.2739/kurumemedj.MS652009. Epub 2019 Mar 11.

Abstract

Background: The role of IL-38, a new member of the IL-1 family, in airway eosinophilic inflammatory conditions such as asthma is unclear. To investigate the role of IL-38 in airway eosinophilic inflammation, an IL-38-gene deficient (KO) murine asthma model was analyzed.

Methods: The numbers of eosinophils and neutrophils, and levels of IL-5, IL-13 and IL-17A protein and mRNA in bronchoalveolar lavage fluid (BALF) and lung tissue were compared between wild-type (WT) and IL-38-KO mice after OVA sensitization and challenge. The effects of additional purified recombinant mouse (rm) IL-38 protein were investigated in the IL-38-KO murine asthma model.

Results: The IL-38 and IL-5 mRNA in WT mice was significantly higher after OVA challenge than after saline challenge (p<0.05). The number of airway eosinophils in IL-38-KO mice was significantly lower than in WT mice after OVA challenge (p<0.01). BALF analysis confirmed the lower number of airway eosinophils in IL-38-KO mice and showed that this was significantly associated with lower IL-5 protein levels (r=0.92, p<0.0001). However, the additional rm IL-38 protein did not neutralize airway eosinophilia in IL-38-KO mice.

Conclusion: IL-38 may enhance airway eosinophilic inflammation in asthma through IL-5 induction.

Keywords: Airway inflammation; Asthm; Cytokine; Eosinophils; IL-38.

MeSH terms

  • Animals
  • Asthma / genetics
  • Asthma / metabolism*
  • Bronchoalveolar Lavage Fluid
  • Crosses, Genetic
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Eosinophilia / genetics
  • Eosinophilia / metabolism*
  • Female
  • Inflammation / genetics
  • Inflammation / metabolism*
  • Interleukin-1 / genetics*
  • Interleukin-1 / metabolism
  • Interleukin-13 / metabolism
  • Interleukin-17 / metabolism
  • Interleukin-5 / genetics*
  • Interleukin-5 / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neutrophils / metabolism
  • Ovalbumin
  • RNA, Messenger / metabolism
  • Recombinant Proteins / metabolism

Substances

  • Il17a protein, mouse
  • Il1f10 protein, mouse
  • Interleukin-1
  • Interleukin-13
  • Interleukin-17
  • Interleukin-5
  • RNA, Messenger
  • Recombinant Proteins
  • Ovalbumin