ABSTRACT
To study the pattern of lymphokines in bleomycin-induced lung injury, T cells were isolated from lung interstitial tissue (LIL), peribronchial lymphatic tissue (PBLT), and bronchoalveolar lavage (BAL) fluid of bleomycin-"sensitive" C57Bl/6 and bleomycin-"resistant" BALB/c mice at 3, 6, and 14 days following intratracheal instillation of bleomycin or saline. After 48 hours in culture, conditioned media were collected and assayed with specific enzyme-linked immunosorbent assay (ELISA) for interferon (IFN)-gamma, interleukin (IL)-2, IL-4 and IL-5. In bleomycin-treated C57B1/6 mice, IFN-gamma production was increased up to 20-fold at 3 and 6 days in LIL, and at 3 days in PBLT lymphocytes. IL-4 production was slightly decreased in LIL and PBLT lymphocytes at 14 days. IL-2 and IL-5 were not changed by bleomycin. In BALB/c mice, IFN-gamma production was increased 5-fold at 14 days, and IL-2 production at 6 days, in LIL but not PBLT. IL-4 and IL-5 were not significantly changed. The increase in IFN-gamma may play a role in the pathogenesis of bleomycin-induced lung injury. Differences in the cytokine pattern between the strains of mice may contribute to the variable strain susceptibility in bleomycin-induced lung injury.
Subject(s)
Bleomycin/adverse effects , Lymphokines/analysis , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/metabolism , Animals , Antimetabolites, Antineoplastic/adverse effects , Bronchi/cytology , Disease Models, Animal , Interferon-gamma/metabolism , Interleukin-4/metabolism , Lymphocytes/cytology , Lymphocytes/metabolism , Lymphokines/metabolism , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Time FactorsABSTRACT
The role of lymphocytes in bleomycin (Bleo)-induced lung injury remains obscure. In normal hamsters, peribronchial lymphatic tissue (PBLT) has been found to contain a large population of T lymphocytes responsive to interleukin 2 (IL-2) but not to IL-4. Lung injury induced by a single intratracheal instillation of Bleo in hamsters has been ameliorated by cyclosporin A (CyA). In the present study, using this model, PBLT-derived lymphocyte function was explored for 28 days after Bleo instillation. Increase in PBLT lymphocytes occurred at five time points investigated, reaching highest values on day +7 (p < 0.0025). Cell proliferation in response to concanavalin A was enhanced, while IL-2 +/- the mitogen had no effect. In contrast to its inactivity in the normal hamster, in the Bleo-injured animal IL-4 alone induced T cell proliferation (p = 0.0077) on day +7. CyA therapy initially suppressed and delayed recovery of the number of lymphocytes and their activation. The results of this study suggest the existence of a vulnerable period in Bleo-induced lung injury and indicate that lymphocytes participate in the pathogenesis of the insult to the tissue. The unresponsiveness to IL-2 and the emergence of cellular response to IL-4 indicate immune deviation in PBLT-derived T cells.
