We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Mycophenolic acid suppresses granulopoiesis by inhibition of interleukin-17 production.
- Authors
von Vietinghoff, Sibylle; Hui Ouyang; Ley, Klaus
- Abstract
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.
- Subjects
MYCOPHENOLIC acid; IMMUNOSUPPRESSIVE agents; TRANSPLANTATION of organs, tissues, etc.; AUTOIMMUNE diseases; COLONY-stimulating factors (Physiology); T cells
- Publication
Kidney International, 2010, Vol 78, Issue 1, p79
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1038/ki.2010.84