Attenuated Airway Eosinophilic Inflammations in IL-38 Knockout Mouse Model

Area of Science:

• Immunology
• Respiratory Medicine
• Inflammation Research

Background:

• The role of Interleukin-38 (IL-38), a member of the IL-1 family, in asthma pathogenesis remains largely unknown.
• Asthma is characterized by airway eosinophilic inflammation, a key feature targeted in therapeutic strategies.

Purpose of the Study:

• To investigate the specific role of IL-38 in the development of airway eosinophilic inflammation in a murine model of asthma.
• To determine if IL-38 influences key inflammatory mediators such as IL-5, IL-13, and IL-17A.

Main Methods:

• Utilized an ovalbumin (OVA)-induced asthma model in both wild-type (WT) and IL-38-gene deficient (KO) mice.
• Quantified eosinophils, neutrophils, and cytokine levels (IL-5, IL-13, IL-17A) in bronchoalveolar lavage fluid (BALF) and lung tissue.
• Administered recombinant mouse IL-38 (rmIL-38) to IL-38-KO mice to assess its direct impact on airway inflammation.

Main Results:

• OVA challenge significantly increased IL-38 and IL-5 mRNA levels in WT mice.
• IL-38-KO mice exhibited significantly reduced airway eosinophilia compared to WT mice post-OVA challenge.
• Lower eosinophil counts in IL-38-KO mice were strongly correlated with decreased IL-5 protein levels.
• Exogenous rmIL-38 administration did not ameliorate airway eosinophilia in the IL-38-KO asthma model.

Conclusions:

• IL-38 appears to play a role in promoting airway eosinophilic inflammation in asthma.
• The mechanism may involve the induction of IL-5, contributing to the inflammatory response.
• Targeting IL-38 or its downstream effects could be a potential therapeutic avenue for managing eosinophilic asthma.