Document Detail


Cyclosporin A enhances the pulmonary granuloma response induced by Schistosoma mansoni eggs.
MedLine Citation:
PMID:  3372226     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The modulating effect of cyclosporin A (CsA) was studied in the immune-based pulmonary granuloma response to Schistosoma mansoni eggs. The extent of the S. mansoni egg-induced inflammation was quantitated biochemically by measuring total units of N-acetyl-beta-D-glucosaminidase (NAG) and total lung DNA. The enzyme NAG was used as a marker for the activity of inflammatory cells such as macrophages and DNA levels were used to quantify the increased cellularity of the lungs. In this model, the inflammatory response is maximal approximately 2 weeks after egg injection. Daily oral administration of CsA at 50 mg/kg during the first 2 weeks of the response dramatically enhanced the levels of pulmonary inflammation. Similar augmentation of the granuloma response was seen when CsA was given from days 0 to 7 but not when dosed from days 8 to 14. The enhancing of CsA was seen in the high-responder strains C57BL/10, B10.BR and CBA and in a lower-responder strain, Balb/c. Both the S. mansoni egg-induced granuloma response and the CsA-induced enhancement were dependent on functional T cells: athymic C57BL/6 nude (nu/nu) mice developed minimal responses to S. mansoni eggs which CsA did not augment, while heterozygous (nu/+) euthymic B6 mice responded to S. mansoni eggs and CsA. It appears in this model system that CsA may inhibit the activity of suppressor inducer or suppressor T cells. Cyclophosphamide, a drug known to reduce suppressor cell function, augmented the egg-induced inflammatory response similar to CsA. The enhancing activities of CsA and cyclophosphamide were not additive, suggesting effects on a common pathway of biologic activity, the generation of suppressor cells. While CsA and cyclophosphamide augmented the inflammatory process, conventional immunosuppressive drug therapies, dexamethasone and BW755c, quantifiably reduced the levels of NAG and DNA. These results demonstrate that CsA, rather than being immunosuppressive, augments this immune-based model of inflammation. In addition, this study shows that pulmonary granulomatous inflammation can be quantified biochemically with assays for both NAG and DNA.
Authors:
J M Metzger; L B Peterson
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Immunopharmacology     Volume:  15     ISSN:  0162-3109     ISO Abbreviation:  Immunopharmacology     Publication Date:    1988 Mar-Apr
Date Detail:
Created Date:  1988-07-08     Completed Date:  1988-07-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7902474     Medline TA:  Immunopharmacology     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  103-15     Citation Subset:  IM    
Affiliation:
Department of Experimental Pathology, Merck Sharp and Dohme Research Laboratories, Rahway, NJ 07065.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cyclosporins / pharmacology*
DNA / analysis
Drug Synergism
Female
Fibrosis
Granuloma / etiology,  immunology,  pathology*
Immunosuppressive Agents / therapeutic use
Inflammation
Lung Diseases, Parasitic / etiology,  immunology,  pathology*
Mice
Mice, Inbred BALB C / immunology
Mice, Inbred C57BL / immunology
Mice, Inbred CBA / immunology
Mice, Nude / immunology
Ovum
Schistosoma mansoni
Chemical
Reg. No./Substance:
0/Cyclosporins; 0/Immunosuppressive Agents; 9007-49-2/DNA

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


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