Effect of Shiftwork on Systemic Markers of Inflammation Sampsa Puttonen, 1,3 Katriina Viitasalo, 2 and Mikko Härmä 1 1 Finnish Institute of Occupational Health, Helsinki, Finland, 2 Finnair Health Services, Vantaa, Finland, 3 Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland Shiftwork is associated with an increased risk of cardiovascular diseases, but the possible role of inflammation in this relationship is not well known. We tested the hypothesis that shiftwork would be associated with higher levels of C- reactive protein (CRP) and increased leukocyte count. We analyzed the cross-sectional associations between work arrangements and low-grade inflammation in 1877 airline-company employees separately for men (n = 1037) and women (n = 840). The participants were classified into five categories according to their work schedule: day workers who have not worked in shifts (referent group), former shiftworkers, 2-shift workers, 3-shift workers, and in-flight workers. In models adjusted for age and recent infectious diseases, CRP levels were higher among male 3-shift workers ( p= .002) and marginally higher in male 2-shift workers ( p= .076). In addition, leukocyte count was higher in 2-shift ( p= .005) and 3-shift ( p= .021) working men. In women, CRP level was higher in 2-shift workers ( p= .028), whereas leukocyte count was lower in flight workers ( p= .005). Any separate adjustment additionally for smoking, education, alcohol consumption, physical activity, and obesity did not substantially affect the results of 2- and 3-shift work. In the fully adjusted model, only the association between 3-shift work and CRP in men ( p= .021) and 2-shift work and leukocyte count in men ( p= .020) and leukocyte count in 3-shift-working women ( p= .044) were significant. Our results suggest that 2- and 3-shift work is associated with increased systemic inflammation and the relationship is relatively independent of the considered risk factors of cardiovascular disease. (Author correspondence: Sampsa.Puttonen@ttl.fi) Keywords: C-reactive protein, Epidemiology, Inflammation, Leukocyte count, Shiftwork, White blood cell INTRODUCTION The development of our modern 24/7 society has in- creased the proportion of irregular work hours. In the European Union (EU) every fifth worker and in China more than one in three workers are employed in shiftwork (Office for Official Publications of the European Commu- nities, 2008). Shiftwork causes disruption of biological rhythms and disturbs sleep and social life, which can negatively influence well being and health (Bambra et al., 2008; Haus & Smolensky, 2006; Tuchsen et al., 1996). The relationship between shiftwork, defined as either work at changing hours of the day or work at con- stant but unusual hours of the day and cardiovascular dis- eases (CVD) has been widely studied over the last decades. Although studies have shown that shiftwork plays a role in the development of CVD (Bøggild & Knuts- son, 1999; Frost et al., 2009), the mechanisms of this association are not well understood (Puttonen et al., 2010). With this respect, inflammation is a plausible, but insufficiently studied, pathophysiological mechanism through which shiftwork may influence the observed risk of atherosclerosis and cancer (Puttonen et al., 2009; Schernhammer et al., 2006). Psychosocial stress as well as experimental stress evoke immunological changes, including increased levels of proinflammatory cytokines and possibly also C-reactive protein (CRP) (Hemingway et al., 2003; Steptoe et al., 2007). Night and shiftwork schedules cause circadian stress, resulting in sleep deprivation and various psychosocial, behavioral, and physiological stress reactions (Puttonen et al., 2010). Both partial and total sleep restriction increase the level of circulating CRP and proinflammatory cytokines (Frey et al., 2007; Meier-Ewert et al., 2004; van Leeuwen et al., 2009). Low-grade systemic inflammation, as measured by CRP and leukocyte count, is an independent risk factor for CVD in working-aged men and women (Fortmann et al., 2004). Of the several inflammatory markers studied, CRP is suggested to be most influential in pre- dicting CVD in apparently healthy adults (Ridker et al., Address correspondence to Sampsa Puttonen, Finnish Institute of Occupational Health, Topeliuksenkatu 41 a A, FIN-00250, Helsinki, Finland. Tel: +358 30 474 2526; E-mail: Sampsa.Puttonen@ttl.fi Submitted May 5, 2010, Returned for revision June 3, 2010, Accepted April 6, 2011 Chronobiology International, 28(6): 528–535, (2011) Copyright © Informa Healthcare USA, Inc. ISSN 0742-0528 print/1525-6073 online DOI: 10.3109/07420528.2011.580869  Chronobiol Int Downloaded from informahealthcare.com by Tyoterveyslaitos on 07/31/11 For personal use only.