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T-cell costimulation blockade is effective in experimental digestive and lung tissue fibrosis.
- Source :
-
Arthritis research & therapy [Arthritis Res Ther] 2018 Aug 29; Vol. 20 (1), pp. 197. Date of Electronic Publication: 2018 Aug 29. - Publication Year :
- 2018
-
Abstract
- Background: We aimed to investigate the efficacy of abatacept in preclinical mouse models of digestive involvement, pulmonary fibrosis, and related pulmonary hypertension (PH), mimicking internal organ involvement in systemic sclerosis (SSc).<br />Methods: Abatacept has been evaluated in the chronic graft-versus-host disease (cGvHD) mouse model (abatacept 1 mg/mL for 6 weeks), characterized by liver and intestinal fibrosis and in the Fra-2 mouse model (1 mg/mL or 10 mg/mL for 4 weeks), characterized by interstitial lung disease (ILD) and pulmonary vascular remodeling leading to PH.<br />Results: In the cGvHD model, abatacept significantly decreased liver transaminase levels and markedly improved colon inflammation. In the Fra-2 model, abatacept alleviated ILD, with a significant reduction in lung density on chest microcomputed tomography (CT), fibrosis histological score, and lung biochemical markers. Moreover, abatacept reversed PH in Fra-2 mice by improving vessel remodeling and related cardiac hemodynamic impairment. Abatacept significantly reduced fibrogenic marker levels, T-cell proliferation, and M1/M2 macrophage infiltration in lesional lungs of Fra-2 mice.<br />Conclusion: Abatacept improves digestive involvement, prevents lung fibrosis, and attenuates PH. These findings suggest that abatacept might be an appealing therapeutic approach beyond skin fibrosis for organ involvement in SSc.
- Subjects :
- Animals
Disease Models, Animal
Female
Fibrosis prevention & control
Humans
Hypertension, Pulmonary pathology
Hypertension, Pulmonary prevention & control
Immunosuppressive Agents pharmacology
Intestines pathology
Lung drug effects
Lung pathology
Lung Diseases, Interstitial pathology
Lung Diseases, Interstitial prevention & control
Male
Mice, Inbred BALB C
Mice, Inbred C57BL
T-Lymphocytes immunology
T-Lymphocytes metabolism
Abatacept pharmacology
Intestines drug effects
Pulmonary Fibrosis prevention & control
T-Lymphocytes drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1478-6362
- Volume :
- 20
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Arthritis research & therapy
- Publication Type :
- Academic Journal
- Accession number :
- 30157927
- Full Text :
- https://doi.org/10.1186/s13075-018-1694-9