OBJECTIVETo investigate the relationship between emotional status, cold-dry environment and long-term immune responses to the stressors, and the potential pathological mechanisms between causative factors of abnormal Savda syndrome (ASS) and the susceptibility to disease; thus to clarify the ASS, and secondly to identify the optimal ASS animal model for further studies on traditional Uighur therapeutical formulations.

METHODSSixty mice were randomly and equally divided into 4 groups: control and 3 stress groups. The cold-dry environment was applied by keeping the mice in a climatic chamber. The emotional stress was induced by the application of the repeated electric foot-shocks in the electric foot-shock apparatus. The mice of the combined stress group underwent the repeated electric foot-shock treatment before being housed in the climatic chamber. The experimental routine was repeated for 21 days. In order to look into endocrine and immune stress responses, ELISA was used to determine the serum levels of the hormones corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), Beta-endorphin (β-END) and corticosterone (CORT), of the cytokines interleukin 2 (IL-2), interleukin 6 (IL-6), interferon-gamma (INF-γ) and tumor necrosis factor-alpha (TNF-α), and of the immunoglobulins immunoglobulin A (IgA), immunoglobulin M (IgM) and immunoglobulin G (IgG). Lymphocyte subsets were analyzed in duplicate in order to determine differences in the T cell ratio.

RESULTSIn the cold-dry environment group, the serum levels of CRH, ACTH and CORT were significantly higher than those of the control group, whereas serum β-END was not found significantly different. In both the repeated electric foot-shock group as well as in the combined stress group the serum levels of CRH, ACTH, β-END and CORT were significantly higher. Compared to the control animals, the serum concentration of INF-γ was significantly lower in all three different stress groups. The serum level of IL-2 was decreased in the combined stress group whereas the serum TNF-α level was significantly higher. The serum IgG level was significantly higher in all three stress groups, whereas the IgA level was lower in both chronic electric foot-shock group and combined stress group. The IgM level was found significantly higher in the combined stress group only. The percentage of CD4(+) cells in peripheral blood was dramatically decreased in mice exposed to colddry environment, chronic electric foot-shock and combined stress, whereas the percentage of the CD8(+) subset was not significantly different. The CD4(+)/CD8(+) ratios were markedly lower in both cold-dry environment group and combined stress group.

CONCLUSIONSCombined stress can cause hyperactivity of the HPA axis, and an imbalance in the Th1/Th2 cell subset may contribute to illustrate the partial pathological mechanisms of ASS. This study identified this animal model of a combination of physical and emotional stress as an optimal model for further studies on ASS and relative therapies.