Inflammation-related muscle weakness and fatigue in geriatric patients I. Beyer a, b, ⁎, R. Njemini b , I. Bautmans a, b , C. Demanet c , P. Bergmann d , T. Mets a, b a Department of Geriatrics, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, B-1090 Brussels, Belgium b Frailty in Aging Research Group (FRIA) & Gerontology Department, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, B-1090 Brussels, Belgium c Department of HLA & Molecular Hematology, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, B-1090 Brussels, Belgium d Department of Nuclear Medicine, CHU Brugmann, Université Libre de Bruxelles (ULB), 4 Place Van Gehuchten, B-1020 Brussels, Belgium abstract article info Article history: Received 16 July 2011 Received in revised form 11 October 2011 Accepted 12 October 2011 Available online 18 October 2011 Section Editor: Christiaan Leeuwenburgh Keywords: Muscle Hsp27 Eotaxin MCP-1 Geriatric patients Inflammation in older persons is associated with muscle wasting, leading to frailty and functional decline. Most studies have focused on IL-6 and TNF-α. In order to further elucidate the underlying mechanisms of muscle wasting and reduced muscle mass and strength we investigated a large panel of cytokines and che- mokines, as well as cytoprotective heat shock proteins (Hsp), and measured lean body mass (LBM) and grip strength (GS), fatigue resistance (FR), and grip work (GW) in 33 geriatric patients (median age 84 years) admitted with acute infection-induced inflammation. Higher expression of Hsp27 without heat challenge (WHC) in circulating monocytes and lymphocytes correlated with better FR (r = 0.363, p b 0.05 and r = 0.602, p b 0.001 respectively) suggesting a protective effect, as Hsp27 is abundant in muscle. On the other hand, higher serum levels of the inflammatory chemokines CCL11/Eotaxin and CCL2/MCP-1 were relat- ed to lower GS and lower LBM (r =-0.393, p b 0.05; r =-0.431, p b 0.05) respectively. Our results point to a complex pattern of pro-and anti-inflammatory substances that interact with skeletal muscle performance during acute inflammation. © 2011 Elsevier Inc. All rights reserved. 1. Introduction The production of pro-inflammatory substances during acute dis- eases, such as infections, leads to unintentional weight loss with dis- proportionate muscle wasting (Morley et al., 2006). This situation has been termed cachexia and is associated with frailty, functional decline and increased mortality (Evans et al., 2008; Morley et al., 2009). Acute cytokine-induced decreases in muscle contractility can occur due to increased production of reactive oxygen species (ROS) and actin–my- osin dissociation in the initial stages of proteolytic pathways before measurable decreases in muscle mass appear (Zoico and Roubenoff, 2002). In a previous study we have demonstrated weaker grip strength and a worse fatigue resistance in hospitalized geriatric pa- tients with inflammation compared to non-inflammatory patients (Bautmans et al., 2005). IL-6 and TNFα have been incriminated in this process, especially at higher age (Stowe et al., 2010). However, concentrations of other pro-inflammatory cytokines and chemokines, such as MCP-1 and IP-10, the prototypes of the CC and CXC chemo- kine families, increase with age (Antonelli et al., 2006) and might play a role in older patients. Cell-protective mechanisms, such as stress-induced production of heat shock proteins (Hsp), are blunted in older patients (Calderwood et al., 2009). In the present study we assessed the relation of a wide range of cyto-/chemokines and Hsp with muscle performance and lean body mass in geriatric patients ad- mitted for acute infection, in order to obtain a better insight in the complexity of inflammation-induced muscle weakness and fatigue. 2. Methods 2.1. Participants Consecutive admissions to an acute geriatric ward of a general teaching hospital in Brussels, Belgium, were screened. To be included patients had to be 70 years of age or older, be admitted for acute in- fection and present serum levels of C-reactive protein (CRP) > 10 mg/L and/or fibrinogen > 400 mg/dL. Exclusion criteria were: in- flammation due to non infectious illness, use of corticosteroids or non-steroidal anti-inflammatory drugs (NSAID) within the past seven days, and being unable to understand or execute the test proce- dures due to cognitive or physical impairments. The use of inhalation corticosteroids, low dose aspirin (as anti-aggregating medication) and paracetamol was allowed. Peripheral venous blood was collected in the morning after over- night fasting. Clinically relevant parameters were immediately deter- mined. Serum was stored at -20 °C for the determination of cyto-/ chemokines and Hsp. EDTA anticoagulated blood was used for imme- diate determination of intracellular Hsp in mononuclear cells. Patients were included after written informed consent from the patient or proxy. The study protocol was accepted by the local ethical committee. Experimental Gerontology 47 (2012) 52–59 ⁎ Corresponding author at: Dienst Geriatrie, UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium. Tel.: +32 2 476 33 07; fax: +32 2 477 63 64. E-mail address: Ingo.Beyer@uzbrussel.be (I. Beyer). 0531-5565/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.exger.2011.10.005 Contents lists available at SciVerse ScienceDirect Experimental Gerontology journal homepage: www.elsevier.com/locate/expgero