Sustained Systemic Levels of IL-6 Impinge Early Muscle Growth and Induce Muscle Atrophy and Wasting in Adulthood
Laura Pelosi,
Maria Grazia Berardinelli,
Laura Forcina,
Francesca Ascenzi,
Emanuele Rizzuto,
Marco Sandri,
Fabrizio De Benedetti,
Bianca Maria Scicchitano,
Antonio Musarò
Affiliations
Laura Pelosi
DAHFMO-Unit of Histology and Medical Embryology, Sapienza University of Rome, Via A. Scarpa, 14, 00161 Rome, Italy
Maria Grazia Berardinelli
DAHFMO-Unit of Histology and Medical Embryology, Sapienza University of Rome, Via A. Scarpa, 14, 00161 Rome, Italy
Laura Forcina
DAHFMO-Unit of Histology and Medical Embryology, Sapienza University of Rome, Via A. Scarpa, 14, 00161 Rome, Italy
Francesca Ascenzi
Department of Clinical and Molecular Medicine, Risk Management Q and A, Sant’Andrea Hospital, “Sapienza” University, 00161 Rome, Italy
Emanuele Rizzuto
Department of Mechanical and Aerospace Engineering, Sapienza University of Rome, 00184 Rome, Italy
Marco Sandri
Veneto Institute of Molecular Medicine, 35129 Padua, Italy
Fabrizio De Benedetti
Division of Rheumatology and Immuno-Rheumatology Research Laboratories, Bambino Gesù Children’s Hospital, 00146 Rome, Italy
Bianca Maria Scicchitano
Istituto di Istologia ed Embriologia, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “Agostino Gemelli”, IRCCS, 00168 Rome, Italy
Antonio Musarò
Laboratory Affiliated to Istituto Pasteur Italia—Fondazione Cenci Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, Sapienza University of Rome, Via Antonio Scarpa, 14, 00161 Rome, Italy
IL-6 is a pleiotropic cytokine that can exert different and opposite effects. The muscle-induced and transient expression of IL-6 can act in an autocrine or paracrine manner, stimulating anabolic pathways associated with muscle growth, myogenesis, and with regulation of energy metabolism. In contrast, under pathologic conditions, including muscular dystrophy, cancer associated cachexia, aging, chronic inflammatory diseases, and other pathologies, the plasma levels of IL-6 significantly increase, promoting muscle wasting. Nevertheless, the specific physio-pathological role exerted by IL-6 in the maintenance of differentiated phenotype remains to be addressed. The purpose of this study was to define the role of increased plasma levels of IL-6 on muscle homeostasis and the mechanisms contributing to muscle loss. Here, we reported that increased plasma levels of IL-6 promote alteration in muscle growth at early stage of postnatal life and induce muscle wasting by triggering a shift of the slow-twitch fibers toward a more sensitive fast fiber phenotype. These findings unveil a role for IL-6 as a potential biomarker of stunted growth and skeletal muscle wasting.
