Search

The present study compared plasma IL-18 levels between sham-operated and adrenalectomized mice following stress to investigate whether the adrenal gland contributes to the elevation of circulating IL-18 during stress. Two hours of stress provoked a robust, stressor-dependent, elevation of IL-18 mRNA and peptide in the adrenal gland in sham-operated mice. Consistently, levels of circulating mature IL-18 increased during stress and remained elevated for up to 6 h after stress. The stress-induced increase in circulating IL-18 was abolished by adrenalectomy. These findings demonstrate that the adrenal gland is required to achieve elevation of circulating IL-18 during stress.

Seasonal changes in day length enhance or suppress immune function in individuals of several mammalian species. Siberian hamsters (Phodopus sungorus) are long-day breeders that adjust reproductive physiology and behavior, body mass, and immune function following exposure to short photoperiods. Photoperiods of intermediate-duration, encountered in nature by juvenile hamsters born in early-spring and by those born in mid-summer, trigger gonadal development in the former cohort and inhibit the onset of puberty in the latter. Divergent reproductive responses to the same intermediate photoperiod depend on a photoperiod history, communicated during gestation. These experiments assessed whether photoperiod history during gestation likewise impacts immunological responses to intermediate photoperiods. Male hamsters were gestated in long photoperiods and remained in long photoperiods postnatally, or were transferred to an intermediate-duration or a short-duration photoperiod; other males were gestated in short days and transferred to an intermediate-duration photoperiod at birth. Long days stimulated, and short days inhibited, somatic and reproductive development; intermediate day lengths either accelerated or inhibited somatic and reproductive development, depending on whether hamsters were gestated in short days or long days, respectively. By contrast, photoperiod during gestation did not affect most immune endpoints. The data suggest that photoperiodic mechanisms that enhance and suppress several aspects of immunity in young-adult hamsters are not responsive to prenatally communicated photoperiod history information.

Splenocytes from socially stressed male mice display functional glucocorticoid (GC) resistance, viz., the antiproliferative effects of GC on lipopolysaccharide (LPS)-stimulated splenocytes is absent. In this study, we investigated changes in the structure and function of the glucocorticoid receptor (GR) in socially stressed animals. Changes of GR at both DNA and RNA levels were excluded. Reduced GR function was restricted to macrophages (CD11b(+)) in association with impaired nuclear translocation of GR after GC stimulation. Consequently, GC failed to block the activation of NF-kappa B in these cells. Thus, impaired nuclear translocation of GR and the lack of transcriptional suppression of NF-kappa B by GC were identified as the molecular mechanisms responsible for the observed GC resistance in spleens of socially stressed mice.

Social stress of group-housed male mice induced a state of functional glucocorticoid (GC) resistance in splenocytes. The following studies examined the effects of paired-fighting (PF) stress on immune cell distribution and function in spleens of male mice. Following six daily PF stress sessions, splenic monocytes and neutrophils increased and lymphocytes decreased. PF also altered the distribution of CD62L and CD11b positive monocytes. Additionally, PF augmented proliferation and lowered the sensitivity of LPS-stimulated splenocytes to the antiproliferative effects of corticosterone, suggesting that PF induced a state of GC resistance in splenocytes. Together, these findings indicate that social stress altered phenotype and function of splenic immune cells. These findings may have implications for the healing of bite wounds that are often associated with social stress in rodents.

Social disruption (SDR) of male mice has been shown to induce a state of functional glucocorticoid (GC) resistance in splenocytes. The present study demonstrated that GC resistance developed following repeated, but not acute exposure to SDR. GC resistance was long-lasting and persisted for at least 10 days after stress. In contrast, SDR did not alter cytokine secretion from peritoneal mononuclear cells treated with corticosterone. These findings suggest that SDR-induced GC resistance may be restricted to specific sites such as the spleen.