Interpersonal Stressors – Proinﬂammatory Cytokine Responses
A PNAS study indicates that negative social interactions may predict levels of proinflammatory cytokines IL-6 and the soluble receptor for tumor necrosis factor-α (sTNFαRII) and their reactivity to a social stressor. Negative social interactions predicted elevated sTNFαRII at baseline, and IL-6 and sTNFαRII 25-min poststressor, as well as total output of sTNFαRII. Competitive social interactions predicted elevated baseline levels of IL-6 and sTNFαRII and total output of both cytokines.
Social relationships and particularly negative and competitive social interactions influence physical health. One way social relationships may influence health is through inflammation. Negative and competitive social interactions represent the most frequent type of stressor experienced in people’s daily lives.
Also, interpersonal stressors involving social threat (e.g., social conflict, evaluation, rejection, isolation, and exclusion) upregulate inflammatory processes and induce several depressive symptoms – this is a central component of the social signal transduction theory of depression.
Cytokine is a general term used for small secreted proteins that are key modulators of inflammation. There are both pro-inflammatory and anti-inflammatory cytokines. The pro-inflammatory cytokines are secreted from Th1 cells, CD4+ cells, macrophages, and dendritic cells. They are characterized by production of several interleukins (IL), IL-1, IL-2, IL-12, IL-17, IL-18, IFN-γ, and TNF-α. The key pro-inflammatory cytokines are IL-1, IL-6, and TNF-α.
Increases in pro-inflammatory cytokines, including IL-6 and TNF-α have been linked to hypertension, cardiovascular and coronary heart disease, depression, and some cancers. People who are socially integrated or have larger social networks have been found to have lower plasma levels of IL-6 and C-reactive protein (CRP).
In the PNAS study Jessica Chiang and colleagues from the Department of Psychology, David Geffen School of Medicine, University of California, Los Angeles, investigated the potential importance of negative, competitive and positive daily interactions on inﬂammatory activity.
The investigators hypothesized that negative and competitive daily interactions would be related to higher basal cytokine levels, and that exposure to negative and competitive social events would be related to increased sensitivity to social threats, reflected in elevated proinflammatory cytokine responses to laboratory stressors.
The authors found that negative and competitive interactions were related to proinflammatory cytokine activity. Negative social interactions were linked to higher baseline levels of sTNFαRII, sTNFαRII and IL-6 responses following a social stressor, and total output of sTNFαRII. The experience of competitive interactions over the 8 d was associated with higher IL-6 (marginally significant) and sTNFαRII at baseline and with greater overall output of both IL-6 and sTNFαRII.
The authors discuss the possible mechanisms involved and the long-term health consequences of these ﬁndings, which suggest that everyday social interactions marked by negativity or competition are predictive of inﬂammatory activity. The results also raise the questions of why daily social experiences are related to inflammation and by what routes.
Chronic stress is known to contribute to a low-grade systemic inflammation, and stress hormones may mediate the link between daily social interactions and inflammation.
Negative social interactions also lead to increases in blood pressure and heart rate, indices of activity of the autonomic nervous system, which is consistent with rodent models showing that social stress increases sympathetic activity. It is quite possible that negative and competitive daily social interactions up-regulate inflammatory activity via the autonomic nervous system.
Whereas negative interactions are predominantly hostile encounters, competitive events may be inherently more variable. However, the reliabilities of positive, negative, and competitive event measures were all high. Nevertheless, despite the high reliability of the competitive events measure, the category included leisure activities, academic/work-related competition, and competing for a person’s attention, which may relate to proinflammatory activity in different ways.
Of note, proinflammatory cytokines were assessed via oral mucosal transudate (OMT), which poses a qualification. sTNFαRII collected via OMT has been validated only in HIV patients. Nevertheless, similar to systemic inflammatory processes, oral inflammatory activity also increases in response to social stress and depression, suggesting a relation between systemic and oral inflammatory activity. At the very least, inflammatory markers measured by OMT reflect peripheral, localized inflammation in the mouth, a critical site for immune response, as it is a primary avenue by which bacteria and viruses can enter and infect the body.
In conclusion, the present results suggest that everyday social interactions marked by negativity or competition are predictive of inflammatory activity. According to the authors the impact of any single such interaction may be minor, cumulatively, however, they may have a sustained effect on inﬂammatory processes and therefore may have implications for mental and physical health outcomes related to inﬂammation.
Source: Proc Natl Acad Sci U S A, 2012, 109:1878. Epub 2012 Jan 23
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