Anti-interleukin-6 receptor antibody (MR16-1) promotes muscle regeneration via modulation of gene expressions in infiltrated macrophages.
BACKGROUND
Although rat anti-mouse IL-6 receptor (IL-6R) antibody (MR16-1) has been reported to effectively ameliorate various tissue damages, its effect on skeletal muscle regeneration has not been determined. Moreover, the localization, persistence and duration of action of this reagent in damaged tissues after systemic administration have not been assessed.


METHODS
The MR16-1 was administered i.p. immediately after cardiotoxin (CTX)-induced muscle damage on mice.


RESULTS
MR16-1 administered i.p. was observed only to the damaged muscle. This delivered MR16-1 was dramatically decreased from 3 to 7days post-injury concomitantly with a reduction of IL-6R expression. This reduction of the MR16-1 level in the damaged muscle was not rescued by additional administration of MR16-1, suggesting the short half-life of MR16-1 was not the factor for the remaining levels. In addition, a significant inhibitory effect of MR16-1 on phosphorylation of the signal transducer and activator of transcription 3 was observed in the macrophage-enriched area of damaged muscle 3days after injury. Finally, the acceleration of muscle regeneration observed at day 7 post-injury following MR16-1 treatment was associated with reduced expression of fibrosis-related genes, such as interleukin-10 and arginase, in the infiltrated macrophages.


CONCLUSIONS
These results suggest that MR16-1 which was found primarily localized in infiltrated macrophages in the damaged muscle might facilitate muscle regeneration via immune modulation.


CONCLUSIONS
These findings are deemed to provide further insight into the understanding not only of MR16-1 treatment on muscle regeneration, but also of the other anti-cytokine treatment on the cytokine-related disease.
Graduate School of Medicine, Osaka University, Japan.
Ryo
R
Fujita
Graduate School of Medicine, Osaka University, Japan.
Fumimori
F
Kawano
Graduate School of Frontier Bioscience, Osaka University, Japan.
Takashi
T
Ohira
Graduate School of Medicine, Osaka University, Japan.
Naoya
N
Nakai
Graduate School of Frontier Bioscience, Osaka University, Japan.
Tsubasa
T
Shibaguchi
Laboratory of Immune Regulation, Wakayama Medical University, Japan.
Norihiro
N
Nishimoto
Graduate School of Medicine, Osaka University, Japan; Graduate School of Frontier Bioscience, Osaka University, Japan. Electronic address: oyoshinobu@gmail.com.
Yoshinobu
Y
Ohira
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001119:Arginase / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D018482:Muscle, Skeletal / Q000293:injuries* / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects* / Q000235:genetics
D000911:Antibodies, Monoclonal; C556062:IL10 protein, mouse; D009124:Muscle Proteins; D019947:Receptors, Interleukin-6; D016753:Interleukin-10; D001119:Arginase
Anti-mouse IL-6 receptor (IL-6R) antibody; Fibrosis; Muscle injury; Muscle regeneration