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 three same-sex non-siblings (Group) or alone (Isolate). Rats were injected with bacterial lipopolysaccharide (Escherichia coli LPS; 150 microg/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-1beta production in all groups, but plasma IL-1beta concentrations were higher and peaked earlier in Isolate relative to Group males, and in Group relative to Isolate females. Furthermore, plasma concentrations of TNFalpha 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.

Conflict of interest statement

Conflict of interest statement: All authors declare that there are no conflicts of interest.

Copyright 2010 Elsevier Inc. All rights reserved.

Figures

Figure 1

Mean (±SEM) hourly change in body temperature of male (A, C) and female (B, D) Wistar rats housed 1/cage (Isolate; panels A and B) or 3/cage (Group; panels C and D) prior to and following treatment with lipopolysaccharide (150 µg/kg i.p.; LPS) or saline (at time 0). Open:filled bars above each plot indicate the daily light:dark cycle. Within each panel: * p < 0.05 vs. saline.

Figure 2

Mean (±SEM) hourly locomotor activity counts of male (A) and female (B) Wistar rats housed 1/cage (Isolate) or 3/cage (Group) prior to and following treatment with LPS (150 µg/kg i.p.) or saline (at time 0). The daily light:dark cycle is depicted by a black and white bar above each graph. Within each panel, * p < 0.05 vs. SAL within Housing condition. Time interval over which LPS values differed pairwise from SAL values within sex (p < 0.05) are indicated along the abscissa with dark bars.

Figure 3

The total number of visits to the food hopper (A) and total duration of time spent eating (B) of male and female Wistar rats housed 1/cage (Isolate) or 3/cage (Group) and treated treatment with LPS (150 µg/kg i.p.) or SAL are presented as the mean (±SEM). Feeding behavior was sampled in 10-min bins, once per h, for the first 10 h (scotophase) following injections. * p < 0.05 vs. SAL value within sex and social condition.

Figure 4

The total number of initiated (A) and received (B) social interactions, and the total duration of time spent in side-by-side social contact (C) of male and female Wistar rats housed 3/cage (Group) and treated with LPS (150 µg/kg i.p.) or saline are presented as the mean (±SEM). Social behavior was sampled in 10-min bins, once per h, for the first 10 h (scotophase) following LPS and saline treatment. Values represent the total frequency or duration over 10 hourly 10-minute bins at baseline (24 hours prior to treatment) and following injection. See Methods for description of behavioral criteria. * p < 0.05 vs. saline value.

Figure 5

Mean (±SEM) plasma concentrations of corticosterone measured by specific EIA. Male and female Wistar rats were housed 1/cage (Isolate) or 3/cage (Group) prior to (A) and following injections (B) (150 µg/kg i.p.). # p < 0.05 vs. SAL value within housing condition and sex. * p < 0.05, male vs. female.

Figure 6

Mean (±SEM) plasma concentrations of IL-1β measured by specific EIA. Male and female Wistar rats were housed 1/cage (Isolate) or 3/cage (Group) prior to and following treatment with LPS (150 µg/kg i.p.). * p < 0.05 vs. Group-male value; # p < 0.05 vs. Isolate-female value.