Cytokine
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In hemorrhagic shock and trauma, patients are prone to develop systemic inflammation with remote organ dysfunction, which is thought to be caused by pro-inflammatory mediators. This study investigates the role of the immuno-modulatory cytokine IL-10 in the development of organ dysfunction following hemorrhagic shock. Male C57/BL6 and IL-10 KO mice were subjected to volume controlled hemorrhagic shock for 3h followed by resuscitation. ⋯ In IL-10 KO mice, pulmonary MPO activity was significantly increased 3 h following resuscitation and after 24 h histological signs of acute lung injury were more apparent than in C57/BL6 mice. In contrast, no significant differences in any liver parameters were detected between IL-10 KO and C57/BL6 mice. Our data indicate that an endogenous IL-10 deficiency augments acute lung but not liver injury following hemorrhagic shock.
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Burn injury is associated with profound inflammation and activation of the innate immune system involving gammadelta T-cells. Similarly, Toll-like receptors (TLR) are associated with activation of the innate immune response; however, it is unclear whether TLR expression is altered in gammadelta T-cells after major burn injury. To study this, male C57BL/6 mice were subjected to burn injury (25% TBSA) and 1 or 7 days thereafter, blood and spleen cells were isolated and subjected to FACs analysis for TLRs and other phenotypic markers (gammadelta TCR, alphabeta TCR, CD69, CD120b). ⋯ The increases in TLR expression were not observed in alphabeta T-cells after burn injury. In conclusion, 24h after burn injury mobilization of gammadelta T-cells with increased TLR expression was observed. This finding suggests that this unique T-cell population is critical in the innate immune response to injury, possibly through the recognition of danger signals by TLRs.
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Randomized Controlled Trial
Effects of insulin therapy on inflammatory mediators in infants undergoing cardiac surgery with cardiopulmonary bypass.
To determine whether insulin administration modulates the systemic inflammatory response in infants undergoing cardiac surgery with cardiopulmonary bypass, 60 infants undergoing cardiopulmonary bypass were randomly assigned into a routine therapy group or to an intensive insulin therapy group with 30 infants in each group. Plasma IL-1beta, IL-6, IL-10, and TNF-alpha levels were determined before anesthesia, at the initiation of cardiopulmonary bypass, and at 0, 6, 12, 24, and 48 h after cardiopulmonary bypass. Nuclear factor-kappaBp65 expression and IkappaB expression in peripheral blood mononuclear cells were also measured by Western blot analysis. ⋯ The expression of Nuclear factor-kappaBp65, which induces the transcription of pro-inflammatory cytokines was significantly attenuated in the intensive insulin therapy group (p<0.05 or <0.01). Meanwhile, the expression of IkappaB, an inhibitor of NF-kappaB, was significantly higher in the intensive insulin therapy group (p<0.05 or <0.01). These results suggested that intensive insulin therapy may attenuate the systemic inflammatory response in infants undergoing cardiopulmonary bypass.
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Opsoclonus-myoclonus syndrome (OMS) is an autoimmune, paraneoplastic, central nervous system disorder, characterized by cerebrospinal fluid (CSF) B-cell expansion and various putative autoantibodies. To investigate the role of B-cell activating factor (BAFF) in OMS and the effect of disease-modifying immunotherapies used to treat it, BAFF was measured by enzyme-linked immunoadsorbent assay in the CSF and serum of 161 children with OMS and 116 pediatric controls. The mean concentration of CSF BAFF and the CSF/serum BAFF ratio were significantly higher in untreated OMS compared to neurological controls. ⋯ Monthly IVIg infusions had no net impact on BAFF levels, and the combination of IVIg with ACTH or steroids did not reduce or enhance their anti-BAFF effects. These data indicate that BAFF production is increased centrally, not peripherally, in OMS, implying astrocytic over production. The novel dose-related central and peripheral anti-BAFF properties of ACTH, especially, have implications for other BAFF-related autoimmune disorders, infectious diseases, and cancers.
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To explore the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in traumatic brain injury (TBI)-induced intestinal inflammatory response and gut barrier dysfunction in the mice. ⋯ Nrf2 plays an important protective role in limiting intestinal inflammatory response and gut barrier dysfunction after TBI.