Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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The purpose of this investigation was to compare the effects of initial resuscitation with HBOC-201 to that of lactated Ringer (LR) solution in the setting of uncontrolled hemorrhage and traumatic brain injury (TBI). Anesthetized immature swine underwent fluid-percussion TBI and liver laceration. During a 75-min "prehospital phase," the animals were resuscitated with HBOC-201, LR solution, or nothing (NON). ⋯ Severity of subarachnoid and intraparenchymal hemorrhages was statistically greater in LR solution-treated animals, but these differences were not likely to be clinically significant. There were no differences in glial fibrillary acidic protein and microtubule-associated protein 2. In this model of combined uncontrolled hemorrhage and TBI, initial resuscitation with HBOC-201 resulted in significant improvements in survival and systemic and cerebrovascular physiological parameters, as well as a reduction in transfusion requirements.
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Previously, we have shown that small arterial trauma is accompanied by a decreased capability of both toll-like receptors (TLRs) 2 and 4 to respond to stimulation with their respective ligands Pam3Cys and LPS. In this study, we assessed whether surgical arterial trauma induces a decrease in the TLR response and investigated the time course of the altered responsiveness. In addition, TLR responsiveness was related to baseline patient characteristics. ⋯ Toll-like receptor 2 and 4 response declines rapidly after arterial trauma in patients undergoing vascular surgery. These results point to a significant role for TLRs in the induction of postoperative immune tolerance. Furthermore, smoking is negatively related to baseline TLR response.
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The IL-1 receptor-associated kinase 1 (IRAK-1) and IRAK-M are key signaling molecules in cellular responses to endotoxin initiated through the Toll-like receptors (TLRs). The aim of this study was to evaluate the effect of age on the modulation of TLRs and IRAK-1 and IRAK-M in peripheral blood mononuclear cells (PBMCs) exposed in vitro to endotoxin under conditions that could induce endotoxin tolerance. Peripheral blood mononuclear cells obtained from young (4- to 6-month-old) and aged (24- to 26-month-old) Brown Norway rats were treated with high-dose LPS, with or without priming with low-dose LPS. ⋯ In contrast, PBMCs from aged rats treated in this manner continued to express measurable levels of IRAK-1 protein. Preconditioning with low-dose LPS caused an increase in both IRAK-M protein and mRNA (P = 0.05) after stimulation with high-dose LPS only in cells from young rats. These phenotypic characteristics of PBMCs from aged rats can interfere with their ability to develop tolerance to endotoxin.
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The long pentraxin 3 (PTX3) is an important element of the innate immune system and has potential as a diagnostic tool in inflammatory conditions. We studied PTX3 in patients admitted to an intensive care unit with severe meningococcal disease and compared it with the short pentraxin C-reactive protein (CRP). Twenty-six patients with meningococcal disease were studied, 17 patients presented with meningococcal septic shock (shock group), and 9 patients presented with meningococcal meningitis or bacteremia (no-shock group). ⋯ PTX3 at admission and PTX3 peak concentration both showed a negative correlation with plasma fibrinogen concentrations. C-reactive protein concentration at admission correlated negatively with disease severity. In conclusion, PTX3 was an early indicator of shock in patients with severe meningococcal disease that followed a pattern of induction distinct from CRP.