Sex-specific social regulation of inflammatory responses and sickness behaviors

Abstract

In many mammals, the availability of familiar conspecifics in the home environment can affect immune function and morbidity. Numerous sex differences exist in immune responses, but whether the social environment impacts the immune system differently in males and females is not fully understood. This study examined behavioral and physiological responses to simulated bacterial infection in adult male and female Wistar rats housed either with 3 same-sex non-siblings (Group) or alone (Isolate). Rats were injected with bacterial lipopolysaccharide (E. coli LPS; 150 µg/kg, i.p.), and behavioral (orectic, locomotor, and social) and physiological (thermoregulatory, cytokine, and corticosterone) inflammatory responses were measured. Among males, LPS-induced fever, suppressed locomotor activity, and inhibited feeding behavior and the magnitude of these responses were greater in Isolate relative to Group housed individuals. In contrast, among females group housing exacerbated behavioral and physiological symptoms of simulated infection. LPS treatments elicited IL-1β production in all groups, but plasma IL-1β concentrations were higher and peaked earlier in Isolate relative to Group males, and in Group relative to Isolate females. Furthermore, plasma concentrations of TNFα and IL-2 were higher in Group relative to Isolate males. Plasma corticosterone concentrations did not vary as a function of social housing conditions. Together, the data indicate that the social environment markedly influences innate immune responses. Group housing exacerbates inflammatory responses and sickness behaviors in females, but attenuates these responses in males. These sex differences are mediated in part by differential effects of the social environment on pro-and anti-inflammatory cytokine production.

The sociality–health–fitness nexus: synthesis, conclusions and future directions

“…In one experiment, the induction of cytokine-mediated inflammation led laboratory rats to spend more time in close contact with familiar cage-mates [88]. Analogous results have been observed in humans.…”

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

“…Hence, in rats, in addition to reducing active social behavior with an unfamiliar conspecific, LPS can also lead to more huddling with familiar cagemates (Yee and Prendergast, 2010). Similarly, juvenile rhesus monkeys injected with low-dose LPS spent more time in close proximity with and clinging to a familiar cage-mate than did vehicle-injected controls (Willette et al, 2007).…”

When is it socially acceptable to feel sick?

“…In zebra finches, group-housing (versus housing in isolation) is associated with reduced expression of sickness behaviour without significant alteration of the inflammatory response as quantified by plasma IL-6 [45], which could be an indication that in certain social contexts animals have some motivation to conceal their sickness, for example, to maintain social status. In male rats, group-housing also attenuates LPS-induced sickness behaviours, whereas in females, group-housing exacerbates these behaviours relative to LPS-injected animals housed in isolation [46]. In an experiment using house finches (Haemorhous mexicanus), infection with the bacterium Mycoplasma gallisepticum caused individuals to become more submissive (i.e.…”

“…Weil et al [38] demonstrated that in mice, maternal aggression towards a virgin male intruder was not changed by an LPS injection at a dose sufficient to induce classical components of sickness behaviour (such as reduced food intake). Both of these experiments show that Taeniopygia guttata (zebra finch) decreased SB in males [45] Rattus novergicus (rat) decreased SB in males, increased in females [46] rspb.royalsocietypublishing.org Proc. R. Soc.…”