Sex differences in the peripheral and central immune responses following lipopolysaccharide treatment in pubertal and adult CD‐1 mice

Abstract

Puberty is a critical developmental period that is characterized by significant brain development. Exposure to stress during this time can alter brain functioning setting the stage for long-lasting behavioural outcomes. The objective of this study was to investigate age and sex differences in the peripheral and central immune responses, along with sickness behaviour, following immune stress. The results showed that LPS treatment increased serum cytokine levels and sickness symptoms in all mice. Pubertal males displayed increased IL-1β concentrations at 2 h and increased IL-6 concentrations at 8 h post-treatment whereas increased concentrations of TNFα, IL-10, IL-12, IL-1β, IFNγ, and IL-6 persisted at 8 and 24 h in adult females. Consistent with peripheral cytokines, pubertal males displayed greater IL-1β, TNFα, and IL-6 mRNA expression in the prefrontal cortex at 2 h, whereas adult males expressed more of the aforementioned cytokines at 8 h compared to saline controls. Adult males also displayed greater IL-1β mRNA expression compared to their female counterparts, and adult females displayed greater TNFα mRNA expression compared to their male counterparts. These results not only provide a better understanding of the age and sex differences in acute immune response, but also show important region- and time-specific differences in the response to an immune challenge, and that the peripheral immune response differs from the central response. This highlights the need to examine immune markers in both the periphery and the central nervous system for an accurate depiction of acute immune response following an immune challenge.

Intranasal Neuropeptide Y Blunts Lipopolysaccharide-Evoked Sickness Behavior but Not the Immune Response in Mice

“…administration of LPS to mice has been reported to enhance the peripheral and cerebral expression of cytokines and to elicit behavioral reactions in a sex-dependent manner [45,46]. Specifically, the enhancement of the circulating levels of IL-1β is more pronounced in adult female than in male mice, whereas the expression of IL-1β in the prefrontal cortex is more pronounced in male than in female mice [46]. It is also noteworthy that NPY pretreatment caused a delayed increase in hypothalamic IL-10 mRNA expression in LPS-injected mice.…”

Programming Effects of Pubertal Lipopolysaccharide Treatment in Male and Female CD-1 Mice

“…Like the stress response, the immune response also appears to be suppressed in pubertal mice compared with adults. Recent findings from our laboratory show that mice treated with LPS during puberty display a reduced immune response as shown by less hypothermia, symptoms of sickness, and proinflammatory cytokines in the blood compared with their adult counterparts (34,35). In contrast to the periphery, LPS treatment induces greater cytokine mRNA expression in various brain regions in pubertal mice compared with adults (35).…”

“…All primers were diluted to a final concentration of 0.3 mM for the real-time PCR. b-Actin was used as the reference/housekeeping gene for all samples as it was not significantly different among experimental groups and has been identified as a reliable housekeeping gene in previous studies (35). For each reaction, the quantitative threshold amplification cycle number was determined, and the 2 2DDquantitative cycle threshold method was used to calculate the relative gene expression of each gene in question (Table I).…”

“…Recent findings from our laboratory show that mice treated with LPS during puberty display a reduced immune response as shown by less hypothermia, symptoms of sickness, and proinflammatory cytokines in the blood compared with their adult counterparts (34,35). In contrast to the periphery, LPS treatment induces greater cytokine mRNA expression in various brain regions in pubertal mice compared with adults (35). Pubertal mice also display different microglia morphology relative to their adult counterparts following LPS challenge (36).…”

“…We predicted that mice pretreated with an immune challenge during puberty would show an attenuated immune response compared with their pretreated saline counterparts and their counterparts pretreated with LPS during early adulthood. We also expected the peripheral immune response to differ from the central immune response as the presence of immune markers in the periphery is not always consistent with central changes (35,55).…”