Countering Inflammation-related Muscle Weakness in Geriatric Patients

Scriptie/masterproef: Doctoral Thesis

Uittreksel

In this thesis we have explored the link between inflammation and muscle parameters in acutely diseased geriatric patients. Furthermore, the possibility of favourably influencing acute inflammation and muscle function by pharmacological treatment has been appraised in a double-blind randomized controlled design.

In chapter one a narrative review of the literature is presented with respect to the impact of sarcopenia in geriatric patients and concerning the role that inflammatory mediators play in the genesis of sarcopenia. The term sarcopenia has been used as an umbrella term including different kinds of muscle wasting that occur in older adults. Inflammation and sarcopenia have been quite consistently linked in cross-sectional, longitudinal and interventional studies. Most information being available concerns IL-6 and TNF-alpha. Furthermore, mechanistic links between inflammatory mediators and muscle protein breakdown have been elucidated.

Chapter two contains a systematic review of the recent literature (January 2010 to July 2011) about chronic low-grade inflammatory profile (CLIP) and age-related sarcopenia. The studies included in this review further strengthen the role of inflammation in age-related muscle wasting.

The possibility to pharmacologically influence muscle weakness and fatigue by direct action on inflammatory pathways is approached in chapter three, where mechanisms of action of classical NSAID are briefly discussed, with special attention to cyclooxygenase(COX)-1 and -2, as well as COX-independent mechanisms.

After a general overview of the rationale and methodology in chapter four, the effects of NSAID treatment with piroxicam on cyto-/chemokines, as well as cyto-protective heat shock proteins (Hsp), are explored in geriatric patients admitted with acute infection (chapter five). The results suggest that piroxicam modulates inflammatory and protective mechanisms, with particular effects demonstrated in peripheral blood monocytic cells (PBMC) on IL-6 and IP-10/CXCL10 that are down regulated, and on Hsp27 that shows increased expression. While serum levels of CRP significantly decreased in patients receiving piroxicam and in patients receiving placebo, these observations indicate that an additional impact on acute inflammation can be obtained by non selective NSAID treatment on top of the expected improvement following antibiotic treatment of the underlying disease.

The links between muscle parameters and a large panel of 25 cyto-/chemokines, as well as two different Hsp, are described in the setting of acute infectious disease in chapter six. The unexpected correlations observed for the chemokines MCP-1/CCL2 and Eotaxin/CCL11 with muscle mass and strength respectively, extend the sparse and recent data from the literature, concerning cell cultures or young human volunteers, that suggest a possible role for these chemokines in skeletal muscle.

We then explored the possibility that specifically targeting inflammation and related cyto-protective mechanisms may influence the evolution of muscle mass and performance (chapter seven). While muscle performance at admission for acute infection was particularly limited, an early initiation of recovery in fatigue resistance and grip work was observed in patients treated with piroxicam, but not with placebo. This improvement persisted after correction for body weight that influences performance in activities of daily living. The recovery in muscle performance was paralleled by improvements in mobility. Short term treatment with piroxicam in this setting appeared to be well tolerated.

The research results are summarized in chapter eight and their possible clinical impact is discussed.
Datum Prijs9 feb 2012
TaalEnglish
Toekennende instantie
  • Vrije Universiteit Brussel
BegeleiderTony Mets (Promotor), Ivan Bautmans (Co-promotor), Rose Njemini (Co-promotor), Leon Verbruggen (Jury), Christel Geerts (Jury), Pierre Van Roy (Jury), Thierry Pepersack (Jury), Tommy Cederholm (Jury) & J. Baeyens (Jury)

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