Effects on muscle performance of NSAID treatment with piroxicam versus placebo in geriatric patients with acute infection-induced inflammation. A double blind randomized controlled trial.
BACKGROUND
Inflammation is the main cause of disease-associated muscle wasting. In a previous single blind study we have demonstrated improved recovery of muscle endurance following celecoxib treatment in hospitalized geriatric patients with acute infection. Here we further evaluate NSAID treatment with piroxicam in a double blind RCT and investigate the role of cytokines and heat shock proteins (Hsp) with respect to muscle performance. We hypothesized that NSAID treatment would preserve muscle performance better than antibiotic treatment alone, by reducing infection-associated inflammation and by increasing expression of cytoprotective Hsp.


METHODS
Consecutive admissions to the geriatric ward were screened. 30 Caucasian patients, median age 84.5 years, with acute infection-induced inflammation and serum levels of CRP > 10 mg/L were included and randomized to active treatment with 10 mg piroxicam daily or placebo. Assessment comprised general clinical and biochemical parameters, 25 cytokines in serum, intra-and extracellular Hsp27 and Hsp70, Elderly Mobility Scale (EMS) scores, grip strength (GS), fatigue resistance (FR) and lean body mass (LBM). Patients were evaluated until discharge with a maximum of 3 weeks after treatment allocation.


RESULTS
EMS scores, FR and grip work (GW), a measure taking into account GS and FR, significantly improved with piroxicam, but not with placebo. Early decreases in IL-6 serum levels with piroxicam correlated with better muscle performance at week 2. Basal expression of Hsp27 in monocytes without heat challenge (WHC) was positively correlated with FR at baseline and significantly increased by treatment with piroxicam compared to placebo. Profound modifications in the relationships between cytokines or Hsp and changes in muscle parameters were observed in the piroxicam group.


CONCLUSIONS
Piroxicam improves clinically relevant measures of muscle performance and mobility in geriatric patients hospitalized with acute infection-induced inflammation. Underlying mechanisms may include modifications in the cytokine network and increases in monocytic expression of cytoprotective Hsp27.


BACKGROUND
ISRCTN: ISRCTN96340690.
Department of Geriatrics, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, B-1090 Brussels, Belgium. ingo.beyer@uzbrussel.be
Ingo
I
Beyer
Ivan
I
Bautmans
Rose
R
Njemini
Christian
C
Demanet
Pierre
P
Bergmann
Tony
T
Mets
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001530:Belgium; D016009:Chi-Square Distribution; D003141:Communicable Diseases / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016207:Cytokines / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D015577:Geriatric Assessment; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018737:Hand Strength; D006360:Heat-Shock Proteins; D006760:Hospitalization; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D018832:Molecular Chaperones; D018763:Muscle Fatigue / Q000187:drug effects*; D053580:Muscle Strength / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D010894:Piroxicam / Q000627:therapeutic use*; D010919:Placebos; D013997:Time Factors; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D010919:Placebos; D010894:Piroxicam