In Sickness and in Health: The Co-Regulation of Inflammation and Social Behavior

Abstract

Although it has commonly been assumed that the immune system and the processes that govern social behavior are separate, non-communicating entities, research over the past several decades suggests otherwise. Considerable evidence now shows that inflammatory processes and social behavior are actually powerful regulators of one another. This review first summarizes evidence that inflammatory processes regulate social behavior, leading to characteristic changes that may help an individual navigate the social environment during times of sickness. Specifically, this review shows that inflammation: (1) increases threat-related neural sensitivity to negative social experiences (eg, rejection, negative social feedback), presumably to enhance sensitivity to threats to well-being or safety in order to avoid them and (2) enhances reward-related neural sensitivity to positive social experiences (eg, viewing close others and receiving positive social feedback), presumably to increase approach-related motivation towards others who might provide support and care during sickness. Next, this review summarizes evidence showing that social behavior also regulates aspects of inflammatory activity, preparing the body for situations in which wounding and infection may be more likely (social isolation). Here, we review research showing: (1) that exposure to social stressors increases proinflammatory activity, (2) that individuals who are more socially isolated (ie, lonely) show increased proinflammatory activity, and (3) that individuals who are more socially isolated show increased proinflammatory activity in response to an inflammatory challenge or social stressor. The implications of the co-regulation of inflammation and social behavior are discussed.

Figure 1

The co-regulation of inflammation and social behavior. The left side of the panel shows that proinflammatory cytokines, through acting on the vagus nerve or the BBB (among other mechanisms) can signal the brain to alter neural sensitivity to the social environment, leading to increases in sensitivity to social threat and social connection. The right side of the panel shows that experiences that threaten social connection (eg, rejection and isolation) can activate certain systems (SNS, sympathetic nervous system; HPA, hypothalamic-pituitary-adrenocortical axis), which can ultimately upregulate proinflammatory activity.

Figure 2

Endotoxin increases amygdala activity specifically to socially threatening images. This figure comes from a prior study (Inagaki et al, 2012) and shows amygdala activity (average of left and right sides) in response to viewing social and non-social, threatening and non-threatening images, displayed separately for endotoxin and placebo subjects.

Figure 3

Endotoxin increases reward-related neural activity in response to viewing images of close others. These data come from a prior study (Inagaki et al, 2015) showing that: (a) endotoxin (vs placebo) led to increased activity in the ventral striatum (VS) in response to viewing images of social support figures and (b) greater increases in IL-6 responses to the endotoxin challenge were associated with greater increases in VS activity to viewing social support figures.

Figure 4

Figure summarizing the effects of experimental inflammatory activity on neural responses, depending on the type of experience (social vs non-social) and the valence of the experience (negative vs positive).

Figure 5

Trait sensitivity to social disconnection is associated with greater increases in inflammatory activity to endotoxin, but not placebo. This figure is reprinted from a prior study (Moieni et al, 2015a), which showed that individuals who reported higher levels of sensitivity to social disconnection showed greater increases in (a) TNF and (b) IL-6 in response to endotoxin (TNF: B=0.077, t=2.84, p<0.01; IL-6: B=0.074, t=2.02, p<0.05) but not in response to placebo (TNF: B=0.021, t=0.868, p=0.39; IL-6: B=−0.005, t=−0.139, p=0.89).