Early inhibition of tumor necrosis factor‐α and interleukin‐6 in muscle tissue as a therapy for dystrophinopathy in mdx mice. Issue 3 (22nd May 2014)

• Record Type: Journal Article
• Authors: Arahata, Hajime; Ohyagi, Yasumasa; Iinuma, Kyoko M.; Tanaka, Masahito; Tateishi, Takahisa; Yamasaki, Ryo; Matsushita, Takuya; Kira, Jun‐ichi
• Is Part Of: Clinical & experimental neuroimmunology. Volume 5:Issue 3(2014)
• Page Start: 371
• Page End: 377
• Publication Date: 2014-05-22
• Subjects: 616.80479
• DOI: 10.1111/cen3.12111
• Languages: English
• ISSNs: 1759-1961

Abstract

<abstract abstract-type="main" id="cen312111-abs-0001"> <title>Abstract</title> <sec id="cen312111-sec-0001" sec-type="section"> <title>Objective</title> <p>Pro‐inflammatory cytokines can exacerbate muscle fiber damage in dystrophinopathy. The aim of the present study was to identify cytokine/chemokine alterations in the muscle tissues of <italic>mdx</italic> mice, a model of dystrophinopathy, and the beneficial effects of anti‐proinflammatory cytokine therapy.</p> </sec> <sec id="cen312111-sec-0002" sec-type="section"> <title>Methods</title> <p>A total of 23 cytokines and chemokines were quantitatively measured in muscle tissues from <italic>mdx</italic> mice by fluorescent bead‐based immunoassay. The <italic>mdx</italic> mice were treated with anti‐tumor necrosis factor‐α (TNF‐α) and anti‐interleukin‐6 (IL‐6) drugs, and their physical condition was evaluated by Rotarod and muscle damage by histopathological analysis.</p> </sec> <sec id="cen312111-sec-0003" sec-type="section"> <title>Results</title> <p>Levels of TNF‐α and IL‐6 were elevated at 14 days (P14), before a transient increase of macrophage and neutrophil‐activating pro‐inflammatory cytokines/chemokines, such as C‐C motif ligand 2 (CCL2), CCL4 and KC (mouse C‐X‐C motif ligand 8 homolog), at P20. Administration of an anti‐TNF‐α drug (etanercept) and an anti‐IL‐6 receptor antibody (MR16‐1) from P7 improved physical performance, and reduced both the area of basophilic fibers that indicated degenerating/regenerating fibers and CD68‐positive macrophage infiltration. Initiating therapy at P7 inhibited the elevation of CCL2, CCL4 and KC more effectively than at P13.</p> </sec> <sec id="cen312111-sec-0004" sec-type="section"> <title>Conclusions</title> <p>The early administration of anti‐TNF‐α and anti‐IL‐6 drugs attenuated muscle fiber degeneration in a mouse model of dystrophinopathy.</p> </sec> </abstract>