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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Trauma/hemorrhagic shock (TH/S) has been associated with inflammation and immunodisorders, leading to immunosuppression, multiorgan dysfunction, and death. However, little is known about the effect of resuscitation with different solutions on the immunological function. To address this issue, groups of male Sprague-Dawley rats were induced with TH/S by fracture in the left femur and continual bleeding to keep the MAP of 30 +/- 5 mmHg for 30 min, followed by resuscitation with 6% hydroxyethyl starch solution (HES), Ringer's lactate solution (RS), or 5% albumin (ALB), and the impact of resuscitation on the activation, differentiation, and survival of CD4 T cells was longitudinally examined after TH/S and resuscitation. ⋯ Treatment with HES or ALB, but not RS, prevented CD4 T-cell apoptosis (sham, 7.23% +/- 3.4%; HES, 10.2% +/- 4.1%; RS, 15.2% +/- 5.4%; ALB, 10.6% +/- 4.3%; 48 h) and nuclear factor-kappaB p65 activation (sham, 0.17 +/- 0.04; HES, 0.34 +/- 0.05; RS, 0.41 +/- 0.09; ALB, 0.25 +/- 0.09; 48 h) induced by TH/S early after resuscitation. These data demonstrated that HES resuscitation modulated the balance of TH1 and TH2 responses and inhibited TH/S-related nuclear factor-kappaB activation and CD4 T-cell apoptosis in TH/S rats. Our findings provide new insights into understanding the TH/S-related immunodisorders and may aid in the design of new therapy for intervention of TH/S.
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Signaling through toll-like receptor 4 (TLR4) plays an obligate role in burn-related myocardial dysfunction. We hypothesized that signaling through CD14, a cellular receptor for endotoxin that lacks a transmembrane domain but is coupled to TLR4, also plays a role in postburn myocardial inflammation and dysfunction. Burn covering 40% total body surface area (or sham burn for controls) was produced in wild-type (WT) and CD14 knockout (KO) as well as vehicle-treated and geldanamycin-treated WT mice (1 microg/g body weight) to inhibit CD14 signaling. ⋯ Relative to sham WT controls, burn trauma in increased cardiac myocyte secretion of inflammatory cytokines (TNF-alpha, IL-1 beta, and IL-6 rose from 59 +/- 10 to 171 +/- 8; 6 +/- 0.2 to 78 +/- 1; and 88 +/- 3 to 170 +/- 12 pg/mL, respectively; P < 0.05) and produced robust cardiac contractile dysfunction (left ventricular pressure and +dP/dt fell from 105 +/- 4 to 73 +/- 5 mmHg and 2,400 +/- 73 to 1,803 +/- 90 mmHg/s; P < 0.05). Inability to signal through the CD14/TLR4 pathway (induced by CD14/KO or inhibition of CD14 expression by administration of geldanamycin) attenuated TNF-alpha, IL-1 beta, and IL-6 production in response to burn injury and improved postburn myocardial contractile function. Our data suggest that signaling through the CD14 pathway plays an obligate role in cardiac inflammation/dysfunction which occurs after major burn injury.