The Mechanisms of Immune Suppression by High-pressure Stress in Mice

Abstract

Abstract The effects of high-pressure stress on the induction of anti-sheep red blood cells (SRBC) and of plaque-forming cells (PFC), and on thymus weight, were studied in BALB/c mice in-vivo and in-vitro. The efficacy of high-pressure stress in suppressing PFC and thymic involution was maximum when the stress was applied 1 h day−1 for 2 days before immunization with SRBC. Both effects were blocked by administration of indomethacin, atropine, naloxone or phentolamine before the first application of stress, whereas hexamethonium and propranolol had no such effect. Hexamethonium, naloxone and propranolol administered before the second application of high-pressure stress blocked both effects. Prostaglandin and acetylcholine given 24 h before application of high-pressure stress caused a marked reduction in PFC count, but not in thymus weight. The reduced PFC count caused by acetylcholine was blocked by pretreatment with indomethacin. When adrenaline was injected 24 h after application of high-pressure stress a marked reduction in PFC was observed, but without thymic involution. When adrenaline was injected 24 h after prostaglandin injection the PFC count was also markedly reduced, but not thymus weight. The decrease in PFC caused by two exposures to stress or one exposure to stress plus injection of adrenaline was blocked by diethylcarbamazine before the second exposure to stress or the injection of adrenaline. In addition, normal spleen cells were induced as suppressor cells when incubated with the serum of stressed mice, but not when supplemented with anti-leukotriene C4, D4 antibody. These data suggest that mice fall into a pre-stress condition via the release of prostaglandin after the first stress, and then immunosuppression is induced in these prestressed mice via the release of leukotriene C4, D4, caused by the activation of the autonomic nervous system by the second exposure to stress.