Am. J. Respir. Crit. Care Med., Vol 153, No. 6, Jun 1996, 1924-1930.
Immunologic alterations in bleomycin-treated mice: role of pulmonary fibrosis in the modulation of immune responses
J Zhu, AM Kaplan and SN Goud
Department of Microbiology and Immunology, University of Kentucky, Lexington 40536-0084, USA.
Among the side effects of bleomycin (BLM), a drug frequently used in the
treatment of lymphomas and squamous-cell carcinomas, is pneumonitis with
pulmonary fibrosis. The most prominent biochemical lesion associated with
pulmonary fibrosis, a chronic debilitating and sometimes fatal disease, is
an increase in the levels of collagen in the lung parenchyma. The
mechanisms involved in the induction of this disease are still unclear,
although results have suggested that the development of fibrosis may be
immunologically mediated. There have, however, been no reports in the
literature on the frequency and function of lymphocytes in the regional and
systemic lymphoid tissues in BLM-induced pulmonary fibrosis. We therefore
conducted a study, in which we inoculated C57Bl/6 mice intratracheally with
BLM or saline, and tested the animals' lymphoid cells for various
cell-mediated and humoral immune responses. The results indicated an
increase in the number of lymphocytes in the lung-associated hilar lymph
nodes, whereas the number of splenic lymphocytes was reduced as compared
with control mice. Moreover, there was a significant inhibition of the
antibody response to sheep erythrocytes in both the spleen and hilar lymph
nodes of BLM-treated mice. Inhibition of the immune system appeared to be
associated with the development of pulmonary fibrosis, and not to result
from BLM toxicity, since the immune response of mice was not inhibited when
they were injected with an identical dose of BLM under conditions that did
not cause pulmonary fibrosis. Moreover, inhibition of splenic antibody
responses was also observed in a hapten-induced model of pulmonary
fibrosis, providing additional evidence that the induction of fibrosis and
not the chemical toxicity of BLM was responsible for the modulation of
immune responses.
