| Studies indicate that stress and depression can modulate immune function. This modulation can manifest in an increase in colds, cancer, and autoimmune disorders. It also appears that people with certain personality traits are more susceptible to the effects of stress; those people may therefore be more prone to alterations in the functioning of their immune system. This research project was designed to investigate the possibility that the WKY rat strain, a putative animal model of depressive behavior, may be used to delineate the mechanisms and pathways involved in the neuro-immune link; more specifically, the population that appears to be more reactive to stress and thus more prone to disease.; Strain differences were observed between WKY and Wistar (WIS) rats in several immune parameters after acute stress, chronic stress, and dexamethasone administration. After acute stress, compared to WIS rats, WKY rats exhibited an exaggerated response in such parameters as alterations in the percentage of circulating monocytes and the magnitude of the decrease in mitogen-stimulated lymphocyte proliferation, yet appeared to be resistant in several measures, such as thymus involution and alterations in the number of total leukocytes. While WKY rats revealed no changes in immune parameters after chronic stress, WIS rats exhibited decreases in both lymphocyte proliferation and interleukin-2 production. In addition to exhibiting corticosterone, non-suppression, similar to what is observed in clinical depression, WKY rats exhibited alterations in lymphocyte and neutrophil percentages after dexamethasone administration, while this effect was not observed in WIS rats. After dexamethasone administration WKY rats again did not exhibit thymus involution, while the effect was seen in WIS rats. It therefore appears that WKY rats react differently to acute stress, chronic stress, and dexamethasone administration in several immune parameters.; Primary cell cultures of T-cells derived from thymuses and spleens of both strains of rats were then incubated with varying concentrations of dexamethasone to determine if the observed strain differences were due to a differential response of this particular cell to glucocorticoids. The EC50 for the suppressive effect of dexamethasone on lymphocyte proliferation was lower in WKY rats for the T-cells isolated from thymus only. As many other pathways may be involved in the differential response to stress observed in the two strains, microarray analysis was then performed to provide a more global view of the differences. Among the observed differences, gene expression for proteins and enzymes involved in the fatty acid metabolism pathway were generally upregulated in WKY rats and not in WIS. Many immune-related genes were also increased in WKY rats, while the same effect was not observed in WIS rats.; These data demonstrate that WKY and WIS rats react differently to varying types of stressors in terms of their immune parameters. Glucocorticoids, as stress hormones, may be involved in the observed differences; however, microarray analysis revealed that many other pathways or mechanisms may be involved. Future experiments aimed at exploring these pathways could provide useful information in delineating neuro-immune pathways specific to WKY rats. |
