Increased systemic inflammation resulting from poor sleep has been hypothesized to be a mechanism through which poor sleep increases risk of morbidity and mortality from

Poor sleep and low social support have each been associated with mortality and morbidity from chronic illness, and a small body of research suggests that the two interact to influence systemic inflammation whereby good social relationships may buffer the relationship between poor sleep and increased inflammation. The current study investigated interactions between sleep and social support in the prediction of inflammation in a clinical population (prehypertensive and hypertensive individuals) at high risk for the development of cardiovascular disease. Using a standardized subjective measure of sleep quality, we found that social support moderated the association between sleep and circulating levels of both IL-6 and CRP, such that poor sleep appeared to confer a risk of increased inflammation only in those participants who also reported low social support. In women, the same relationship was observed for TNF-a. These results extend previous findings into a clinical population and also demonstrate that sleep quality and social support interact in the prediction of two previously uninvestigated clinically relevant inflammatory markers (CRP and TNF-a). High levels of perceived social support may compensate for the negative health impact of poor sleep quality and vice versa. Descriptors: Sleep quality, Social support, Interleukin 6, C-reactive protein, Tumor necrosis factor-a Chronically elevated levels of inflammatory proteins have been associated with myriad negative health outcomes (Pradhan, Manson, Rifai, Buring, & Ridker, 2001). For example, levels of C-reactive protein (CRP) are predictive of the development of cardiovascular disease (CVD), and have been linked to ischemic stroke, vascular mortality, and death (Danesh et al., 2004; Pradhan et al., 2001). Additionally, in large, population-based studies, relatively high levels of the inflammatory markers interleukin-6 (IL-6) and tumor necrosis factor (TNF)-a are predictive of morbidity and mortality (Aggarwal, Gupta, & Kim, 2012; Bruunsgaard et al., 2003; Harris et al., 1999). There is a degree of inconsistency in the literature regarding associations between individual markers and health outcomes, indicating the potential influence of moderating factors. Individuals with prehypertension and hypertension are at high risk for developing CVD, and the population has established levels of low-grade systematic inflammation, which contributes to disease development (Blake, Rifai, Buring, & Ridker, 2003). Due to the high risk for individuals with hypertension/prehypertension to progress to more serious cardiovascular problems, understanding modifiable variables that affect known risk factors, such as inflammation, is important. Levels of circulating inflammatory proteins are influenced by a number of biopsychosocial factors, including sleep. Disturbed sleep, ranging from chronic insomnia to experimental sleep deprivation, along with objectively measured sleep indices, has been robustly associated with elevated inflammation (Grandner, SandsLincoln, Pak, & Garland, 2013; Motivala, 2011). Poor subjectively assessed sleep quality, characterized by tiredness on waking and through the day, not feeling rested and restored on waking, and/or experiencing numerous nighttime awakenings (Harvey, Stinson, Whitaker, Moskovitz, & Virk, 2008) has also been associated with inflammation, such that worse sleep quality has been linked with higher circulating CRP, IL-6, and increased IL-6 production in response to stimulation with lipopolysaccharide (Friedman, 2011; Friedman et al., 2005; McDade, Hawkley, & Cacioppo, 2006; This work was supported by the Alberta Children’s Hospital Research Institute (LMT), NIH grants HL44915 (to PJM), University of California San Diego Clinical and Translational Science Award UL1TR000100, and P60 MD00220 (San Diego EXPORT Center Grant). Thanks to Delaine Ammaturo and Kathleen Wilson for their help in preparing the data. Address correspondence to: Lianne Tomfohr, Department of Psychology, University of Calgary, 2500 University Drive, NW, Calgary, AB, T2N 1N4, Canada. E-mail: ltomfohr@ucalgary.ca 1689 Psychophysiology, 52 (2015), 1689–1697. Wiley Periodicals, Inc. Printed in the USA. Copyright VC 2015 Society for Psychophysiological Research DOI: 10.1111/psyp.12549 Okun, Hall, & Coussons-Read, 2007; Okun, Roberts, Marsland, & Hall, 2009; Prather et al., 2009). Increased systemic inflammation resulting from poor sleep has been hypothesized to be a mechanism through which poor sleep increases risk of morbidity and mortality from CVD (Grandner et al., 2013; Simpson & Dinges, 2007). While experiencing poor sleep quality appears to increase markers of systemic inflammation and confer risk of morbidity and mortality, a number of studies have shown that social support, or “the perception or experience that one is loved and cared for by others, esteemed and valued, and part of a social network of mutual assistance and obligations” (Wills, 1991) confers an opposite, protective effect (Holt-Lunstad, Smith, Baker, Harris, & Stephenson, 2015; Holt-Lunstad, Smith, & Layton, 2010). Individuals lacking in social ties or social integration have higher risk of mortality from numerous diseases, including CVD (Holt-Lunstad et al., 2010, 2015). Low levels of social support have been associated with elevations in inflammatory proteins (Kiecolt-Glaser, Gouin, & Hantsoo, 2010). Social support not only has direct associations with health, but also appears to work as a moderator of the relationship between stress and health, such that high levels of social support have been shown to buffer the negative impact of stressors on health outcomes (Bowen et al., 2013; Steptoe, 2000). There is some evidence that social support also moderates the relationship between poor sleep and inflammation (Friedman, 2011; Friedman et al., 2005; O’Connor et al., 2009). For example, in a study of women aged 61 to 90, Friedman et al. (2005) found that participants who reported poorer sleep efficiency had higher levels of IL-6, but social support buffered the relationship between poor sleep and inflammation. In fact, the only women with elevated IL6 in the study reported both poor sleep quality and low social engagement (Friedman et al., 2005). These findings were recently extended to 1,229 participants from a national sample of adult Americans. Again, social engagement moderated the association between sleep complaints with both IL-6 and the soluble adhesion molecule E-selectin (Friedman, 2011). Gender is another potential moderator in the complicated relationship between sleep, social support, and inflammation. A body of work suggests that disrupted sleep may be more robustly related to inflammation in women (Irwin, Carrillo, & Olmstead, 2010; M. A. Miller et al., 2009; Suarez, 2008). Additionally, laboratory research suggests that in response to social negativity (e.g., marital conflict) women have stronger neuroendocrine and cardiovascular responses than men, suggesting that potentially the relationship between social support and inflammation may also be stronger in women (Kiecolt-Glaser & Newton, 2001; Pietromonaco, Uchino, & Dunkel Schetter, 2013). However, there are some contradictory findings concerning the interaction between gender, sleep, and social support on the outcome of inflammation. For example, research from Friedman (2011) suggested that the interaction between sleep quality and social support on IL-6 was stronger in men than in women. The hypothalamic-pituitary-adrenal (HPA) axis is a system that could hypothetically underlie the complicated relationship between sleep, social support, and inflammatory processes. The HPA axis plays an important role in regulating and controlling immune responses (Spies, Straub, Cutolo, & Buttgereit, 2014). Sleep and social support both have relationships with HPA function, and worsening sleep quality and poor social support are both associated with small but meaningful changes in HPA activation (Balbo, Leproult, & Van Cauter, 2010; Cole, 2008). Potentially, either good sleep or good social support may promote balance in the HPA system and reduce levels of systematic inflammation. In this study, we investigated if social support and sleep quality interacted to predict inflammation in a clinical population with hypertension/prehypertension. Consistent with research examining relationships between social support and inflammation, we examined the potential moderating impact of gender (Kiecolt-Glaser & Newton, 2001; O’Connor et al., 2009). In addition to levels of IL-6, we also investigated two outcome variables (TNF-a and CRP) that have not been previously studied. CRP is particularly important due to its clinical utility as a predictive variable for the development of CVD (Ridker, 2003). We hypothesized that in this sample (a) worse subjective sleep quality would be associated with elevated levels of inflammatory biomarkers, and (b) the relationships would be moderated by levels of perceived social support, such that higher social support would attenuate the relationship between sleep quality and inflammation. Given conflicting findings concerning a potential three-way interaction between gender, social support, and sleep quality in the prediction of inflammation, we conducted exploratory analyses of a potential moderating role of gender, but did not make an a priori hypothesis about the nature of this effect.