Introduction Systemic cytokines produced by contracting skeletal muscles may affect the onset and severity Dynasore of intensive care unit (ICU)-acquired weakness after critical illness. study the 36 participants received 20 min of once-daily in-bed or out-of-bed activity using an established early progressive mobility protocol after physiologic stability had been demonstrated for ≥4 hr in the ICU. Blood samples were drawn on 3 consecutive days beginning on the day of study enrollment for serum cytokine quantification. Results IL-8 IL-15 and TNF-α were highly variable and consistently elevated in participants compared to normal healthy adults. About 1/3 of participants were positive for significant muscle weakness at discharge from ICU. Repeated values of mean postactivity IL-8 serum values were significantly associated only with ADL following ICU discharge. There were no significant associations with repeated values of mean postactivity IL-15 or TNF-α serum values and outcomes. Conclusion Results provide preliminary data for exploring the potential effects of elevated serum values IL-8 and IL-15 Dynasore in muscle health and TNF-α for muscle damage including effect sizes to calculate the sample sizes needed for future studies. (Henriksen Green & Pedersen 2012 Pedersen Akerstrom Nielsen & Fischer 2007 which may alter the course of ICUAW by decreasing muscle damage promoting muscle repair Dynasore and reducing cognitive impairment (Makowshi 2012 Philippou Maridaki Theos & Koutsilieris 2012 Myokines contribute to signaling pathways for muscle fiber regeneration and remodeling and modify cytokine production in the liver and circulating white blood cells. For example interleukin (IL)-8 acts as an attractant to neutrophils and macrophages necessary to remove damaged myofibrils and stimulates new capillary formation essential to muscle repair and growth (Pedersen et al. 2007 IL-8 is also associated with delirium in adults in the ICU and delirium significantly impacts patients’ ability to participate in activity (van den Boogaard et al. 2011 Another myokine muscle-derived IL-15 can stimulate accumulation of protein needed for muscle growth and decrease the rate of protein breakdown (Loell & Lundberg 2011 Systemic inflammation and critical illness-induced cytokines have been implicated in the pathological onset and severity of ICUAW (Bloch Polkey Griffiths & Kemp 2012 Lipshutz & Gropper 2013 Sustained cytokinemia is associated with complications of multiple organ failure and chronic critical illness including skeletal muscle derangements (Dimopoulou et al. 2008 Grander & Dunser 2010 For example proteolysis in muscle cells is enhanced or activated by tumor necrosis factor-α (TNF-α) a cytokine commonly elevated in critical illness (Loell & Lundberg 2011 Makowshi 2012 Vesali et al. 2010 Researchers have reported that serum TNF-α also known as cachexin was increased in patients with reduced skeletal muscle cross-sectional area and peripheral muscle strength (Anker Steinborn & Strassburg 2004 Frost & Lang 2005 Kim Cho & Hah 2012 Loell et al. 2011 Smart & Steele 2011 The purpose of this exploratory research was to determine the serum Dynasore levels of three cytokines associated with skeletal muscle activation damage and repair-IL-8 IL-15 and TNF-α-among patients receiving mechanical ventilation for more than 48 hr and to examine the relationships between these cytokines Dynasore and the outcomes of patient muscle strength activities of daily living (ADLs) duration of mechanical ventilation and length of ICU stay. We specifically hypothesized that IL-8 and IL-15 would be directly associated with increased activity and that elevated levels of TNF-α would be associated with reduced activity. In addition because there is a potential link between muscle activity and cognition we explored delirium as an outcome (Banerjee Girard & Pandharipande 2011 Zaal & Slooter 2012 Method In this prospective repeated measures exploratory investigation participants were mechanically ventilated adults who received a DIAPH2 once-daily progressive mobility protocol. We have reported the main findings and complete sample characteristics of the parent study elsewhere (Winkelman et al. 2012 The institutional review board approved the study and subsequent serum analyses and all participants or their designated surrogates completed informed consent procedures. The overall consent rate for patients approached to participate in this study was 75% with surrogates providing 96% of these consents. Parent study procedures included collection of blood samples at rest and.