Neutralization of tumor necrosis factor-alpha action delays but does not prevent lung injury induced by alloreactive T helper 1 cells.
Transplantation
; 70(1): 39-43, 2000 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-10919572
ABSTRACT
BACKGROUND:
Lung injury occurs frequently after allogeneic bone marrow transplantation in association with graft-versus-host disease, an immune response that involves both cellular and cytokine components. In a murine model, we recently showed that cloned alloreactive T helper (Th)1 cells can cause lung injury associated with increased production of tumor necrosis factor (TNF)-alpha by alveolar macrophages (J Immunol 1998; 161 1913).METHODS:
To evaluate the role of TNF-alpha in this model, we injected in vitro-activated Th1 cells into the following (1) recipients deficient in receptors for TNF; (2) C57BL/6 control mice; (3) C57BL/6 mice, pretreated with soluble TNFRIIFc (a dimorphic high-affinity TNF antagonist); (4) mice expressing TNFRIIFc transgene under control of the surfactant apoprotein C promoter (SPCTNFRIIFc); and (5) wild-type littermate controls (C57BL/6) (n=3-6 mice/group).RESULTS:
At 1 and 3 days after i.v. Th1 cell transfer, recipients were killed for analysis of lung histology, bronchoalveolar lavage (BAL) protein, and BAL cell counts. Control mice (wild type) at day 1 after injection had a mild to moderate mononuclear perivasculitis and increased interstitial cellularity. At day 3, lesions were more severe and perivasculitis also involved larger veins. TNFR-deficient mice had normal lung or minimal lung inflammation at day 1. At day 3, perivasculitis of medium-sized vessels was present, but there was no apparent involvement of larger veins. Results in mice treated with soluble TNFRIIFc and transgenic mice (SPCsTNFRIIFc) were similar to controls. BAL protein and BAL cell counts did not differ between any of the experimental groups.CONCLUSIONS:
We conclude that lung inflammation induced by Th1 cells may be only delayed when TNF-alpha action is blocked. The persistence of abnormalities indicates that other proinflammatory pathways are involved in injury caused by these cells.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator de Necrose Tumoral alfa
/
Células Th1
/
Pulmão
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Transplantation
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Estados Unidos