Gender, race/ethnicity, personality, and interleukin-6 in urban primary care patients

Abstract

Gender, race/ethnicity, and personality are markers of significant psychosocial and biological variability. Each may have implications for allostatic load and resulting inflammatory processes, yet findings have been largely mixed. We investigated whether women, minorities, and those higher in Neuroticism and lower in Extraversion were at risk for elevated circulating levels of the pro-inflammatory cytokine interleukin (IL)-6 in a sample of 103 middle aged and older urban primary care patients. Regression analyses controlling for age, education, current depression levels, and chronic medical conditions revealed that women, minorities, and individuals lower in Extraversion had higher circulating levels of IL-6. Analyses of more specific personality traits revealed that the sociability and positive emotions components of Extraversion were unassociated with IL-6, but the activity facet—reflecting dispositional vigor and energy—was robustly associated with IL-6. The difference between high (+1 Standard Deviation (SD)) and low (−1 SD) trait activity was sufficient to shift IL-6 levels beyond a previously established high risk cut-point in both white and minority women. These findings suggest that while broad group differences between genders and races/ethnicities exist, personality represents an important source of individual differences in inflammation within groups. Future work should examine to what extent IL-6 levels are linked to temperament or genetic activity levels vs. physical activity itself, and whether IL-6 levels may be reduced by boosting regular activity levels in demographic segments such as women and minorities who appear susceptible to greater inflammation.

Introduction

Gender, race/ethnicity, and individual differences in personality are powerful sources of variation in both psychosocial and biological attributes. Yet the extent to which each is associated with underlying inflammation remains unclear. In this paper, we focus specifically on gender, racial ethnic, and personality variation in the inflammatory cytokine interleukin (IL)-6, because it is an important indicator of allostatic load (De Martinis et al., 2005, Franceschi et al., 2000), included in allostatic load composites (Glei et al., 2007), and hence theoretically linked to stress-related factors which may differ by gender, race/ethnicity, and personality. We note that IL-6 was not originally included in allostatic load composites. It has, however, been show to be highly predictive of mortality (Grunewald et al., 2006, Harris et al., 1999), with mortality risk reportedly doubling at levels of 3.19 picograms per milliliter (pg/ml) (Harris et al., 1999). We also focus on a middle aged and older sample, given the cumulative nature of chronic stress adaptation and systemic inflammation (De Martinis et al., 2005), and on the urban primary care population, given the large minority representation often served by these clinics (Fiscella and Williams, 2004).

Prior reports on gender differences in IL-6 have been mixed. O’Connor et al. (2007) reported higher levels of IL-6 in lipopolysaccharide (LPS)-stimulated monocytes from women compared to men (mean age of 36.2 years). In contrast, others have observed a small but significant increase in LPS-stimulated production of IL-6 in young adult males compared to females (Von Aulock et al., 2006), and another study conducted in young adults found no significant gender differences in levels of serum IL-6 (Yang et al., 2007). Others report higher levels of IL-6 among women in older samples (Grunewald et al., 2006). Suarez (2008) also recently found that sleep may account to some degree for gender differences in inflammation.

Differences in serum IL-6 have also been observed in racially-diverse women over the age of 65, with higher levels of IL-6 observed in African American women compared to Caucasians (Allison et al., 2006, Walston et al., 2005). In contrast, no significant differences in serum IL-6 were observed in African Americans versus Caucasians in a mixed gender sample aged 70–79 (Yaffe et al, 2003). If such differences in inflammation do exist however, they may constitute one conceivable explanation for general susceptibility, or the notion that individuals of disadvantaged socioeconomic status (SES) or disenfranchised groups show increased susceptibility to illness (Berkman and Kawachi, 2000). Furthermore, immune function is strongly influenced by psychosocial factors related to stress and coping (Coe and Laudenslager, 2007), and increased stressors such as perceived discrimination frequently encountered by historically disenfranchised groups (Williams et al, 1997) have been hypothesized to increase allostatic load and resulting inflammation (Carlson and Chamberlain, 2005).

Race/ethnicity and gender represent general demographic group markers. However, considerable individual variation in inflammation may exist within genders and racial/ethnic groups. Five Factor Model (FFM) personality dimensions (McCrae and Costa, 2003), representing the primary axes of individual differences in psychological and behavioral dispositions, index variation in stress, coping, and genetic parameters potentially relevant to immune function and inflammation (Coe and Laudenslager, 2007, Segerstrom, 2000, Segerstrom, 2003). Neuroticism has been linked to exaggerated HPA axis responses to stressors (Eysenck and Eysenck, 1985), and appears associated with higher resting cortisol (Miller et al., 1999), lower antibody response to vaccination for hepatitis B (Marsland et al., 2001) and influenza (Phillips et al., 2005), and lower resistance to a common cold virus after infection (Cohen et al., 2003b). Extraversion is thought to be associated with a lower threshold for sympathetic arousal (Eysenck and Eysenck, 1985, Geen, 1997), and greater natural-killer cell cytotoxity (Miller et al., 1999). Specific Extraversion components of sociability (Cohen et al., 2003a) and positive emotions (Cohen et al., 2003b) are also associated with resistance to common cold, while the latter is also associated with higher antibody titers in response to hepatitis B vaccination (Marsland et al., 2001). One study in an older, partly depressed sample found positive associations between Neuroticism, but not Extraversion and IL-6 (Bouhuys et al., 2004). Other studies have variously reported associations between IL-6 and positive affect (Prather et al., 2007), IL-6 and specific aspects of negative affect such as depression and cynicism that may be a function of poor health behaviors (Sjögren et al., 2006), and no associations between trait negative affect and IL-6 (Marsland et al., 2007).

We examined whether IL-6 varied between gender and/or racial/ethnic groups in a diverse urban primary care patient population. Although prior results have been mixed, we hypothesized that women and minority patients would show higher circulating levels of IL-6, as such differences have appeared at least as often as not in prior studies. We also hypothesized that higher Neuroticism and lower Extraversion would be associated with higher IL-6. In other words, we suspected that while gender and/or race/ethnicity would mark general group differences in inflammation, personality would index individual variability in inflammation within gender and racial/ethmic groups, corresponding to independent effects for each factor. We also explored all 2 and 3 way interactions between these factors.