title: Pro-inflammatory capacity of classically activated monocytes relates positively to muscle mass and strength.
abstract: In mice, monocytes that exhibit a pro-inflammatory profile enter muscle tissue after muscle injury and are crucial for clearance of necrotic tissue and stimulation of muscle progenitor cell proliferation and differentiation. The aim of this study was to test if pro-inflammatory capacity of classically activated (M1) monocytes relates to muscle mass and strength in humans. This study included 191 male and 195 female subjects (mean age 64.2 years (SD 6.4) and 61.9 ± 6.4, respectively) of the Leiden Longevity Study. Pro-inflammatory capacity of M1 monocytes was assessed by ex vivo stimulation of whole blood with Toll-like receptor (TLR) 4 agonist lipopolysaccharide (LPS) and TLR-2/1 agonist tripalmitoyl-S-glycerylcysteine (Pam₃Cys-SK₄), both M1 phenotype activators. Cytokines that stimulate M1 monocyte response (IFN-γ and GM-CSF) as well as cytokines that are secreted by M1 monocytes (IL-6, TNF-α, IL-12, and IL-1β) were measured. Analyses were adjusted for age, height, and body fat mass. Upon stimulation with LPS, the cytokine production capacity of INF-γ, GM-CSF, and TNF-α was significantly positively associated with lean body mass, appendicular lean mass and handgrip strength in men, but not in women. Upon stimulation with Pam₃Cys-SK₄, IL-6; TNF-α; and Il-1β were significantly positively associated with lean body mass and appendicular lean in women, but not in men. Taken together, this study shows that higher pro-inflammatory capacity of M1 monocytes upon stimulation is associated with muscle characteristics and sex dependent.
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Karel G M
authors.initials: KG
authors.lastname: Beenakker
authors.forename: Rudi G J
authors.initials: RG
authors.lastname: Westendorp
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: de Craen
authors.forename: Pieternella E
authors.initials: PE
authors.lastname: Slagboom
authors.forename: Diana
authors.initials: D
authors.lastname: van Heemst
authors.forename: Andrea B
authors.initials: AB
authors.lastname: Maier
mesh_terms: D000368:Aged; D015992:Body Mass Index; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008074:Lipoproteins / Q000276:immunology / Q000494:pharmacology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D012737:Sex Factors; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000276:immunology
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008074:Lipoproteins; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D007371:Interferon-gamma
keywords: cytokines; gender differences; handgrip strength; inflammation; innate immunity; macrophage; monocyte; skeletal muscle