Document Detail


Immunologic alterations in bleomycin-treated mice: role of pulmonary fibrosis in the modulation of immune responses.
MedLine Citation:
PMID:  8665057     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
J Zhu; A M Kaplan; S N Goud
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  153     ISSN:  1073-449X     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  1996 Jun 
Date Detail:
Created Date:  1996-08-08     Completed Date:  1996-08-08     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1924-30     Citation Subset:  AIM; IM    
Affiliation:
Department of Microbiology and Immunology, University of Kentucky, Lexington 40536-0084, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bleomycin / adverse effects*
Cell Division / drug effects
Cells, Cultured / drug effects
Female
Hydroxyproline / drug effects,  metabolism
Interleukin-2 / metabolism
Lymphocyte Subsets / drug effects
Lymphocytes / cytology,  drug effects
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Phenotype
Pulmonary Fibrosis / chemically induced,  immunology*,  metabolism
Spleen / cytology,  drug effects
Grant Support
ID/Acronym/Agency:
R01-ES06363/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Interleukin-2; 11056-06-7/Bleomycin; 51-35-4/Hydroxyproline

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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