Persistent interleukin-2 activity and molecular evidence for expression of lymphotoxin in the hapten-immune model for pulmonary interstitial fibrosis.
The hapten-immune model for pulmonary fibrosis shows that a specific T-cell-mediated immune response is essential for the induction of a nonresolving fibrosis. Here, we report results from studies that identify soluble factors released by activated T lymphocytes that might mediate long-lasting fibrosis. Pulmonary fibrosis was induced by priming hamsters for contact hypersensitivity responses with an epicutaneous application of 2,4,6-trinitro-1-chlorobenzene (TNCB) in carrier and challenging intratracheally (IT) 5 days later with a single dose of the soluble form of the immunizing hapten. Bronchoalveolar lavage fluid was harvested at various time points after IT challenge and assayed for tumor necrosis factor (TNF) and interleukin-2 (IL-2) bioactivity. After IT challenge with the sensitizing hapten, only the immune animals contained IL-2 activity in the bronchoalveolar lavage fluid. TNF activity was detected in lungs of both immune and nonimmune animals. Interestingly, the TNF activity was significantly higher (P less than 0.05) in nonimmune challenged than in immune challenged animals on day 5. Molecular hybridization studies showed that a similar amount of TNF-alpha mRNA was expressed in adherent cells from both groups. The nonadherent subpopulation of mononuclear cells harvested from challenged-immune animals expressed TNF-beta (lymphotoxin) mRNA. These data show, for the first time, an association of lymphotoxin with the appearance of pulmonary fibrotic disease in an animal model for pulmonary fibrosis. These observations are consistent with the postulates that lymphotoxin and IL-2 participate in the immunopathogenesis of hapten-immune induced pulmonary fibrosis and that TNF-alpha is associated with the healing of the fibrotic process initiated by toxic lung injury.
Garcia
H
H
Department of Medicine, University of Miami School of Medicine, Florida 33101.
Salter-Cid
L
L
Stein-Streilein
J
J
D000818:Animals; D015152:Blotting, Northern; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism; D006224:Cricetinae; D004195:Disease Models, Animal; D005260:Female; D006241:Haptens / Q000276:immunology*; D007376:Interleukin-2 / Q000378:metabolism*; D008233:Lymphotoxin-alpha / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D008647:Mesocricetus; D011658:Pulmonary Fibrosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000302:isolation & purification / Q000378:metabolism
D006241:Haptens; D007376:Interleukin-2; D008233:Lymphotoxin-alpha; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha