Chronic stress induced duration dependent alterations in immune system and their reversibility in rats

The objective was to find out whether severity of stress effects on immunity increases with duration of exposure and recovery depends on duration of exposure. Adult male rats (n = 30) were subjected to restraint (1 h) followed by forced swimming exercise (15 min) after a gap of 4 h daily for 2, 4 and 8 weeks and allowed to recover for 6 weeks after each exposure period. Exposure of rats to stress resulted in duration dependent significant decreases in leukocyte count, phagocytic indices of neutrophils, number of bone marrow stem cells and serum levels of IL-12 and increases in apoptotic index of peripheral blood mononuclear cells and serum levels of IL-10. The alterations in counts of neutrophils, total immunoglobulin content, phagocytic index, apoptotic index of peripheral blood mononuclear cells and serum levels of IL-10 returned to control levels in recovery group rats of 2 and 4 weeks exposure but not in that of 8 weeks exposure. However, alterations in number and apoptotic index of bone marrow stem cells returned to control levels in 2, 4 and 8 weeks stress recovery groups. The results for the first time reveal that increase in duration of exposure results in more severe damage in immune system and that shorter the exposure period, faster the recovery. In addition, in vitro study for the first time showed that corticosterone causes apoptosis of peripheral blood mononuclear cells and bone marrow stem cells in dose dependent manner. Hence death of leukocytes and their stem cells is the major cause of stress induced immune dysfunction.