4.5 Article

Identification of plasma interleukins as biomarkers for deflazacort and omega-3 based Duchenne muscular dystrophy therapy

Journal

CYTOKINE
Volume 102, Issue -, Pages 55-61

Publisher

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.cyto.2017.12.006

Keywords

Cytokines; Dystrophy; Mdx; Omega-3; Plasma biomarkers

Funding

  1. Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [302831/2013-4, 303320/2013-3]
  2. Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2014/04782-6]
  3. FAPESP [12/15492-3, 2013/00312-2]
  4. CNPq [302831/2013-4, 303320/2013-3]
  5. Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [12/15492-3] Funding Source: FAPESP

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Duchenne muscular dystrophy (DMD) is a progressive and fatal disease, characterized by the absence of dystrophin, muscle degeneration and cardiorespiratory failure. Creatine kinase is the classic marker to screen for DMD. However, other markers are needed to follow disease progression and to evaluate the response to therapy over longer periods. In the present study, we aim to identify interleukins in the plasma of the mdx mice model of DMD that could serve as biomarkers to monitor dystrophy progression, at distinct stages of the disease (1, 3 and 8 months of age). We used deflazacort and omega-3 therapies to validate the biomarkers studied. Plasma levels of TNF-alpha and TGF-beta were increased in mdx mice in relation to control, at all times studied. Differences in IFN-gamma and IL-10 contents, comparing mdx x CTRL, were detected only at the early stage (1 month). IL-6 decreased at 3 and 8 months and IL-13 increased at 8 months in the mdx compared to control. Deflazacort and omega-3 reduced the plasma levels of the pro-inflammatory (TNF-alpha, INF-gamma, IL-6) and pro-fibrotic (IL-13 and TGF-beta) interleukins and increased the plasma levels of IL-10. It is suggested that TNF-alpha and TGF-beta in plasma would be the best markers to follow disease progression. IL-6, INF-gamma and IL-10 would be suitable markers to the earlier stages of dystrophy and IL-13 a suitable marker to the later stages of dystrophy.

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