Document Detail


Mycophenolic acid suppresses granulopoiesis by inhibition of interleukin-17 production.
MedLine Citation:
PMID:  20375992     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mycophenolic acid is a commonly used immunosuppressant after organ transplantation and in autoimmune diseases; however, myelosuppression is a major complication despite its largely favorable side-effect profile. Mycophenolic acid targets inosine monophosphate dehydrogenase, which is essential for T-cell proliferation. The T-cell cytokine interleukin-17 (IL-17 or IL-17A) and its receptor maintain normal neutrophilic granulocyte numbers in mice by induction of granulocyte-colony-stimulating factor. To test whether mycophenolic acid induces neutropenia by inhibiting IL-17-producing T cells, we treated C57Bl/6 mice with mycophenolate-mofetil (the orally available pro-drug) and found a dose-dependent decrease in blood neutrophils. This myelosuppressive effect was completely abolished in mice that lack the IL-17 receptor. Mycophenolic acid delayed myeloid recovery after bone marrow transplantation and decreased the percentage of IL-17-producing T cells in the spleen and thymus, and inhibited IL-17 production in human and mouse T cells in vitro. Injection of IL-17 during mycophenolic acid treatment overcame the suppression of the circulating neutrophil levels. Our study shows that mycophenolic acid suppresses neutrophil production by inhibiting IL-17 expression, suggesting that measurement of this interleukin might be useful in estimating the risk of neutropenia in clinical settings.
Authors:
Sibylle von Vietinghoff; Hui Ouyang; Klaus Ley
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-07
Journal Detail:
Title:  Kidney international     Volume:  78     ISSN:  1523-1755     ISO Abbreviation:  Kidney Int.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-16     Completed Date:  2010-09-22     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  0323470     Medline TA:  Kidney Int     Country:  United States    
Other Details:
Languages:  eng     Pagination:  79-88     Citation Subset:  IM    
Affiliation:
Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA. sibylle@liai.org
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Differentiation / drug effects,  immunology
Colony-Stimulating Factors / immunology,  pharmacology
Cytokines / immunology,  pharmacology
Female
Granulocyte Colony-Stimulating Factor / immunology,  metabolism,  pharmacology
Humans
Immunosuppressive Agents / immunology,  pharmacology
Interleukin-17 / immunology,  metabolism*,  pharmacology
Leukopoiesis / drug effects,  immunology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mycophenolic Acid / analogs & derivatives,  immunology,  pharmacology*
Neutropenia / immunology
Neutrophils / drug effects,  immunology,  metabolism
Receptors, Interleukin-17 / immunology
T-Lymphocytes / immunology,  metabolism
Chemical
Reg. No./Substance:
0/Colony-Stimulating Factors; 0/Cytokines; 0/Immunosuppressive Agents; 0/Interleukin-17; 0/Receptors, Interleukin-17; 143011-72-7/Granulocyte Colony-Stimulating Factor; 24280-93-1/Mycophenolic Acid; 9242ECW6R0/mycophenolate mofetil

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


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