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May 20, 2026

C34-26 Preventive Effect of Thymic Stromal Lymphopoietin Inhibition on Pulmonary Inflammation and Vascular Remodeling in a Lps-exacerbated Chronic Allergic Model

RRR F RighettiHospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo LCL D CamargoUniversidade de São Paulo PCP CanedoHospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

Puntos clave

This study aims to evaluate the effects of TSLP blockade on pulmonary inflammation and vascular remodeling in a chronic allergic asthma model.
Used 84 male BALB/c mice divided into six groups for treatment assessments.
Induced chronic inflammation via ovalbumin sensitization and subsequent LPS exposure.
Conducted histological and immunohistochemical analyses to quantify inflammation and remodeling markers.
Significantly reduced respiratory resistance in the TSLP blockade group (Rrs: 120.8 ± 31.0%) compared to untreated group (459.7 ± 33.0%), p < 0.05.
Polymorphonuclear infiltrates decreased from 3.6 ± 0.3 in OVA to 1.8 ± 0.2 in OVA+anti-TSLP.
TGF-β positive cells decreased from 3.3 ± 0.3 in OVA to 1.78 ± 0.07 in OVA+anti-TSLP.

Resumen

Abstract Rationale Asthma is a chronic inflammatory disease marked by airway obstruction, hyperresponsiveness, and inflammation. Thymic stromal lymphopoietin (TSLP), a key cytokine in Th2/Th17 responses, contributes to airway and vascular remodeling. Although TSLP modulates inflammation and hyperresponsiveness, its role in pulmonary vascular remodeling remains unclear. This study evaluated the acute effects of TSLP blockade on pulmonary inflammation and vascular remodeling in a murine model of chronic allergic asthma exacerbated by lipopolysaccharide (LPS). Methods Eighty-four male BALB/c mice (20–25 g) were divided into six groups (n = 14): saline (SAL), SAL+anti-TSLP, OVA, OVA+anti-TSLP, OVA+LPS, and OVA+LPS+anti-TSLP. Chronic inflammation was induced by ovalbumin (OVA) sensitization (days 1 and 14) and aerosol exposure (days 22–28). LPS (0.1 mg/mL) was instilled intratracheally 24 h after the last OVA challenge. Mice received 20 µg of anti-TSLP intranasally 1 h before LPS exposure. Respiratory mechanics were assessed with the FlexiVent system following methacholine challenge. Histological and immunohistochemical analyses quantified perivascular polymorphonuclear infiltration, collagen, and markers of remodeling (TGF-β, VEGF, endothelin) and inflammation (IL-1β, IL-5, IL-17). Data were analyzed by one-way ANOVA with Holm–Sidak post hoc tests (p 0.05). Results Rrs decreased in OVA (459.7 ± 33.0%) vs. OVA+anti-TSLP (120.8 ± 31.0%) and in OVA+LPS (719.6 ± 104.8%) vs. OVA+LPS+anti-TSLP (136.3 ± 23.4%). Ers decreased in OVA (334.4 ± 70.3%) vs. OVA+anti-TSLP (32.3 ± 9.7%) and in OVA+LPS (266.6 ± 90.5%) vs. OVA+LPS+anti-TSLP (85.6 ± 14.2%). Polymorphonuclear infiltrates decreased in OVA (3.6 ± 0.3) vs. OVA+anti-TSLP (1.8 ± 0.2) and in OVA+LPS (7.4 ± 0.1) vs. OVA+LPS+anti-TSLP (4.2 ± 0.2). Collagen fibers decreased in OVA (19.9 ± 0.7) vs. OVA+anti-TSLP (12.2 ± 0.7) and in OVA+LPS (21.8 ± 1.2) vs. OVA+LPS+anti-TSLP (16.1 ± 1.3). TGF-β–positive cells decreased in OVA (3.3 ± 0.3) vs. OVA+anti-TSLP (1.78 ± 0.07) and in OVA+LPS (3.5 ± 0.2) vs. OVA+LPS+anti-TSLP (1.63 ± 0.12). VEGF-positive cells reduced in OVA (3.2 ± 0.2) vs. OVA+anti-TSLP (0.16 ± 0.03) and in OVA+LPS (5.6 ± 0.4) vs. OVA+LPS+anti-TSLP (0.14 ± 0.01). Endothelin-positive cells decreased in OVA (3.0 ± 0.3) vs. OVA+anti-TSLP (0.16 ± 0.03) and in OVA+LPS (6.1 ± 0.4) vs. OVA+LPS+anti-TSLP (0.21 ± 0.02). IL-1β, IL-5, and IL-17–positive cells showed similar reductions, confirming that TSLP inhibition consistently attenuates airway inflammation and remodeling. Conclusions Preventive TSLP inhibition reduced airway hyperresponsiveness, inflammation, and vascular remodeling in a murine model of chronic allergic asthma exacerbated by LPS. This abstract is funded by: FAPESP (2018/02537-5)

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