Sublethal hemorrhage induces tolerance in animals exposed to cecal ligation and puncture by altering p38, p44/42, and SAPK/JNK MAP kinase activation.

Background: We have shown that SLH induces tolerance to endotoxin in vivo and in vitro, and is associated with alterations in MAP kinase (p38, p44/42, and SAPK/JNK) activation and TNF production. This study investigates the effect of sublethal hemorrhage (SLH) on cecal ligation and puncture (CLP) polymicrobial sepsis and examined the effect of the bioflavinoid, curcumin, a MAP kinase inhibitor, on this relationship. Materials and Methods: Sprague-Dawley rats underwent SLH (hemorrhage and MAP = 30 mm Hg for 15 min, with shed blood returned) or sham operation. After 24 h, rats had CLP (cecal base ligation with double puncture). Survival was determined ± curcumin pretreatment (n = 10/group). Lung tissue, serum, and bronchoalveolar lavage (BAL) fluid were obtained 30 min after SLH and 4 and 12 h after CLP (n = 8/group). Lung tissue was analyzed for p38, p44/42 SAPK/JNK, and HSP-70 phosphorylation (Western). Lung myeloperoxidase (MPO) activity was measured as an index of neutrophil infiltration. TNF ELISA was ...