Abstract Rationale Interleukin-33 (IL-33) is an alarmin involved in the recruitment of inflammatory cells in asthma. Although its inhibition modulates inflammatory responses, the effects of IL-33 blockade have not been evaluated in experimental models of asthma exacerbated by lipopolysaccharide (LPS). Methods Forty-eight male BALB/c mice were divided into five groups: SAL+anti-IL-33, OVA, OVA+anti-IL-33, OVA+LPS, and OVA+LPS+anti-IL-33. Sensitization and challenge with ovalbumin (OVA) were performed in the respective groups, and LPS (0.1 mg/mL) was administered intratracheally 24 h before the end of the 29-day protocol to induce exacerbation. Mice in the treated groups received four doses of 3.6 µg of anti-IL-33 according to the experimental design. At the end of the protocol, animals were anesthetized and tracheostomized for methacholine (MCh)-induced airway hyperresponsiveness assessment and bronchoalveolar lavage fluid (BALF) collection. Total and differential cell counts were performed on BALF to assess airway inflammation. Cytokine concentrations of interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-13 (IL-13), and interleukin-33 (IL-33) were quantified using the Enzyme-Linked Immunosorbent Assay (ELISA). Data are expressed as mean ± standard error of the mean (SEM) and were analyzed by one-way ANOVA followed by the Holm-Šidák test, with p 0.05 considered significant. Results Anti-IL-33 treatment attenuated the maximal response to MCh of respiratory system resistance (Rrs, cmH2O·s/mL) and elastance (Ers, cmH2O/mL). Rrs and Ers were reduced in OVA+anti-IL-33 (Rrs: 0.22 ± 0.25, Ers: 0.41 ± 0.09) and OVA+LPS+anti-IL-33 (Rrs: 0.26 ± 0.02, Ers: 0.40 ± 0.09) compared to OVA (Rrs: 1.27 ± 0.65, Ers: 0.96 ± 0.30) and OVA+LPS (Rrs: 1.00 ± 0.34, Ers: 1.05 ± 0.20) (p 0.05). BALF analysis showed lower total cell counts (×104 cells/mL): OVA+anti-IL-33 (10.67 ± 3.12) and OVA+LPS+anti-IL-33 (10.41 ± 3.02) versus OVA (20.49 ± 1.13) and OVA+LPS (27.95 ± 9.65). Eosinophils and macrophages were also reduced (p 0.05). ELISA confirmed decreased Th2 cytokines and IL-33 levels: OVA+anti-IL-33 (IL-4: 0.10 ± 0.02, IL-5: 0.09 ± 0.01, IL-13: 0.07 ± 0.01, IL-33: 0.20 ± 0.01) and OVA+LPS+anti-IL-33 (IL-4: 0.08 ± 0.01, IL-5: 0.09 ± 0.01, IL-13: 0.07 ± 0.01, IL-33: 0.18 ± 0.01) versus OVA (IL-4: 0.14 ± 0.02, IL-5: 0.14 ± 0.01, IL-13: 0.11 ± 0.01, IL-33: 0.24 ± 0.02) and OVA+LPS (IL-4: 0.15 ± 0.01, IL-5: 0.09 ± 0.01, IL-13: 0.07 ± 0.01, IL-33: 0.18 ± 0.01) (p 0.05). Conclusions IL-33 inhibition reduced airway inflammation and improved lung mechanics in a murine model of asthma exacerbated by LPS. This abstract is funded by: FAPESP (2022/01776-1), LIM-20-HC-FMUSP
Campos et al. (Fri,) studied this question.