Short CommunicationPositive affective style covaries with stimulated IL-6 and IL-10 production in a middle-aged community sample
Introduction
It is well documented that psychological factors can influence the onset and progression of inflammatory diseases, including upper respiratory infection, atherosclerosis, rheumatoid arthritis, and asthma (Cohen et al., 2003, Everson-Rose and Lewis, 2005, Wright et al., 2005, Zautra et al., 1994). Most literature has focused on the detrimental impact of negative emotions on disease susceptibility and the course of illness. In contrast, an emerging literature suggests that dispositional positive affect (PA) may play a protective role in health, perhaps by rendering individuals less vulnerable to inflammatory disease. For example, a recent experimental study found that individuals who characterize themselves as happy, pleased, relaxed, and lively are less susceptible to upper respiratory infection (common cold virus) when compared with participants with less happy dispositions (Cohen et al., 2003). Moreover, no relationship between negative emotional style and infection was observed, nor could these findings be attributed to other factors including age, sex, education, negative affect, or virus-specific antibody status before challenge.
Pathways linking PA to inflammatory disease susceptibility remain unclear; however, possibilities include both behavioral and immune mechanisms. Behaviorally, PA has been linked to a number of healthy lifestyle choices that affect immune function (Kiecolt-Glaser and Glaser, 1988), including better sleep quality and exercise (Bardwell et al., 1999, Cohen et al., 2003, Myers and Diener, 1995). Recent attention has also focused on the possibility that dispositional PA is related to aspects of innate immune function that may influence host susceptibility to inflammation (see review by Marsland et al., 2007). In this regard, the viral challenge study conducted by Cohen and colleagues found higher PA to be associated with less production of the pro-inflammatory cytokine interleukin (IL)-6 in nasal secretions in response to infection, with IL-6 partially mediating the association of PA and upper respiratory disease (Doyle et al., 2006). These findings provide initial evidence that dispositional PA is related to a diminished local inflammatory response, as measured by the production of the IL-6 and thus may decrease susceptibility to infectious disease.
An inflammatory response begins when monocytes/macrophages are activated by pathogens or tissue damage to release pro-inflammatory cytokines, including IL-6, IL-1β, and tumor necrosis factor (TNF)-α. Pro-inflammatory cytokines, in turn, stimulate the recruitment and activation of leukocytes to the site of injury, and the systemic release of acute phase proteins (Black and Garbutt, 2002), such as C-reactive protein and fibrinogen. The magnitude of pro-inflammatory cytokine response to immune activation is critical; insufficient response may leave the organism more vulnerable to infection, and excessive response can increase risk for inflammatory diseases. A number of mechanisms suppress macrophage activation and prevent the excessive production of pro-inflammatory cytokines, including the local release of anti-inflammatory mediators, such as IL-10, by activated immune cells. It remains to be determined whether PA covaries with production of this anti-inflammatory mediator.
The goal of the following study is to further explore the relationship between trait levels of PA and susceptibility to inflammation by examining whether trait positive emotional style is associated with the capacity of immune cells to produce the cytokines IL-1 β, IL-6, TNF-α, and IL-10 following in vitro stimulation with lipopolysaccharide (LPS) among a community sample of relatively healthy mid-life volunteers. Consistent with Cohen et al. (2003), we define PA as feelings that reflect a level of pleasurable engagement with the environment (Clark et al., 1989). Based on existing findings, we expect dispositional PA to be inversely associated with production of pro-inflammatory cytokines, potentially resulting in decreased susceptibility to inflammatory conditions. We also explore the relationship between PA and the production of the anti-inflammatory cytokine, IL-10.
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Participants
Participants were 146 community volunteers (57.5% male, 95.2% Caucasian) between the ages of 30 and 54, enrolled in the Adult Health and Behavior (AHAB) project, a registry of behavioral and biological measurements from community volunteers recruited by mass mail solicitation in Allegheny County, Pennsylvania. All eligible participants reported being in good general health (including no history of myocardial infarction, asthma, cancer treatment in the past year, or psychotic illness). In
Results
Means and standard deviations for demographic variables, psychosocial characteristics and cytokine production are presented in Table 1. As expected, when compared with unstimulated samples, whole blood stimulation with LPS induced an increase in the levels of all 4 inflammatory mediators. Correlational analyses showed that men produced higher levels of stimulated IL-6, TNF-α, and IL-10 than women (p’s < .04). Stimulated cytokine levels were unrelated to medication usage with the exception of
Discussion
This study provides preliminary evidence of a modest association between dispositional PA and LPS-stimulated production of the pro- and anti-inflammatory cytokines IL-6 and IL-10 in a nonpatient sample of community volunteers. Consistent with an emerging literature showing PA associated with better objective health (Pressman and Cohen, 2005), we found that PA was inversely associated with stimulated production of IL-6, a measure of inflammatory potential. This association persisted after
Acknowledgments
This study was supported by a Central Research Development Grant provided by the Vice Provost for Research in the Office of the Provost at the University of Pittsburgh (ALM) and by Grants P01HL40962 from the National Heart Lung and Blood Institute (SBM) and NR008237 from the National Institute of Nursing Research (ALM) and a National Institute of Health fellowship HL007560 (AAP). The expert technical assistance of Ramasri Sathanoori, MS and Adele Marrangoni at the University of Pittsburgh
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