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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monocyte deactivation has been identified as a major factor of immunosuppression in sepsis and is associated with a loss of surface human leukocyte antigen-DR (HLA-DR) expression on circulating monocytes. Using flow cytometry, quantitative reverse transcription-polymerase chain reaction, we investigated this phenomenon in septic patients. We confirmed the early loss of monocyte HLA-DR expression in all infected patients and demonstrated that this persistent lowered expression at Day 6 correlated with severity scores, secondary infection, and death. This phenomenon occurred at a transcriptional level via a decrease in the class II transactivator A (CIITA) transcription. Furthermore, these abnormalities correlated with the high cortisol levels observed in sepsis and not with those of other putative factors such as catecholamines or interleukin-10. Finally, in vitro studies evidenced that glucocorticoids decrease HLA-DR expression at a transcriptional level via a decrease in CIITA mRNA levels, mainly by down modulating its isoforms I and III. We conclude that in human sepsis, the loss of HLA-DR expression on circulating monocytes is associated with a poor outcome. We suggest that the high endogenous cortisol level observed in septic shock may be a possible new factor involved in the loss of HLA-DR expression on monocytes via its effect on HLA-DR and CIITA transcription.
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PMID:Monocyte human leukocyte antigen-DR transcriptional downregulation by cortisol during septic shock. 1502 60

Transfusion-related acute lung injury (TRALI) is an underreported complication of transfusion therapy, and it is the third most common cause of transfusion-associated death. TRALI is defined as noncardiogenic pulmonary edema temporally related to transfusion therapy. The diagnosis of TRALI relies on excluding other diagnoses such as sepsis, volume overload, and cardiogenic pulmonary edema. Supportive diagnostic evidence includes identifying neutrophil or human leukocyte antigen (HLA) antibodies in the donor or recipient plasma. All plasma-containing blood products have been implicated in TRALI, with the majority of cases linked to whole blood, packed RBCs, platelets, and fresh-frozen plasma. The pathogenesis of TRALI may be explained by a "two-hit" hypothesis, with the first "hit" being a predisposing inflammatory condition commonly present in the operating room or ICU. The second hit may involve the passive transfer of neutrophil or HLA antibodies from the donor or the transfusion of biologically active lipids from older, cellular blood products. Treatment is supportive, with a prognosis substantially better than most causes of clinical acute lung injury.
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PMID:Transfusion-related acute lung injury: a review. 1600 80

Pre-term neonates are at high risk to develop early-onset sepsis which possibly is caused by an immature immune system. Monocytes play a pivotal role as professional phagocytic and antigen-presenting cells in the innate immunity. In the present study, we investigated in monocytes from cord blood the expression of human leukocyte antigen (HLA)-DR as a marker for antigen-presenting capability, the expression of the high-affinity receptor for IgG (FcgammaRI/CD64), and the capacity to phagocytize non-opsonized Escherichia coli. We compared 70 infants in three groups according to their gestational age (group I: 20 very low birth weight infants (VLBWI), 24-31 weeks of gestation; group II: 25 pre-term infants, 32-36 weeks of gestation, and group III: 25 term neonates). The expression of CD64 as well as the phagocytic capacity of monocytes from cord blood were highest in VLBWI (p < 0.05 and p < 0.01, respectively). In contrast, HLA-DR expression was significantly (p < 0.05) diminished in VLBWI, which possibly leads to a reduced antigen-presenting capacity. We conclude that monocytes have different functional properties during gestational aging, which perhaps participate in the high incidence of infections in VLBWI.
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PMID:Monocyte switch in neonates: high phagocytic capacity and low HLA-DR expression in VLBWI are inverted during gestational aging. 1561 Mar 64

Multiple trauma patients have an impaired immune system and thus frequently develop life-threatening septic complications. Because there is an ongoing debate on which are the most predictive immunologic parameters of clinical outcome, we prospectively studied 19 multiple trauma patients with sepsis (mean age, 38.7 +/- 15.8 years; mean Injury Severity Score, 40.6 +/- 11.6) over a period of 14 days. The following parameters were measured daily after admission to the intensive care unit: ex vivo lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-alpha) production, monocyte human leukocyte antigen (HLA)-DR expression, constitutive interleukin (IL) 6 secretion, white blood cell count, and C-reactive protein. In addition, procalcitonin, neopterin, LPS-binding protein, and constitutive TNF-alpha secretion were measured every third day. Immediately after trauma, all patients had significantly lower levels of HLA-DR and ex vivo LPS-stimulated TNF-alpha secretion than healthy controls (n = 7; P < 0.001). On the day after clinical diagnosis of sepsis, before any other parameter differed between survivors (n = 13) and nonsurvivors (n = 6), ex vivo LPS-induced TNF-alpha secretion was significantly lower (P < 0.05) in nonsurvivors than in survivors. We conclude that ex vivo LPS-induced TNF-alpha production is an earlier predictor of clinical outcome in multiple trauma patients with sepsis than monocyte HLA-DR expression, constitutive IL-6 secretion, or any other parameter assessed.
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PMID:Lipopolysaccharide-induced tumor necrosis factor alpha production and not monocyte human leukocyte antigen-DR expression is correlated with survival in septic trauma patients. 1652 50

Transfusions are not without risk. One of the side effects of transfusions is the development of transfusion-induced immunomodulation (TRIM)--primarily immunosuppression, but also a strong proinflammatory effect. This may be the cause of acute lung injury (TRALI), multiorgan failure (MOF), transfusion related acute-graft-versus-host-disease (TR AGvHD), as well as of the development of secondary nosocomial infections, mostly pulmonary infections, sepsis and wound infections, and also of elevated number of tumour relapses in oncological patients. The causes of TRIM development are the induction of microchimerism, different cells and also soluble factors--complement components, such as C3a, soluble HLA-I and HLA-II molecules (HLA--human leukocyte antigen), soluble Fas ligand (sFasL), and others. The immunosuppressive potential of blood products grows with the time of their storage and becomes highest in non-leukoreduced blood products stored for a long time. In view of possible adverse effects of a transfusion, the expected benefit should be balanced against possible risks.
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PMID:[Transfusion-induced immunomodulation and infectious complications]. 1716 18

This study aimed to investigate changes in the expression of human leukocyte antigen-DR (HLA-DR) on CD14+ monocytes in the peripheral blood of burn victims with delayed resuscitation in relation to the development of sepsis, and the effect of carbachol in vitro. The study population comprised 25 people with burns of at least 30% of total body surface area and delayed resuscitation, and 20 healthy volunteers as controls. Peripheral blood was collected on post-burn days 1, 3, 7, 14 and 28. When 7 participants developed sepsis, their peripheral blood was drawn on 2 consecutive days. Expression of HLA-DR on CD14+ monocytes in peripheral blood of burned participants was lower than that of controls, and fell further with the development of sepsis, when the rate and concentration of tumour necrosis factor-alpha (TNF-alpha) rose above those of controls and burned participants without sepsis. Expression of HLA-DR on CD14+ monocytes was negatively correlated with interleukin-10 (IL-10) levels on post-burn days 1, 7 and 28. In vitro, HLA-DR expression on monocytes also decreased with lipopolysaccharide (LPS) stimulation, but after treatment with carbachol, rose in a concentration-dependent manner. Thus expression of HLA-DR on CD14+ monocytes may be a useful parameter for monitoring the immune function of burn victims with and without sepsis. Carbachol significantly inhibited LPS-induced immunosuppression in human monocytes in vitro.
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PMID:Low HLA-DR expression on CD14+ monocytes of burn victims with sepsis, and the effect of carbachol in vitro. 1853 34

Sepsis causes over 200,000 deaths yearly in the US; better treatments are urgently needed. Administering bone marrow stromal cells (BMSCs -- also known as mesenchymal stem cells) to mice before or shortly after inducing sepsis by cecal ligation and puncture reduced mortality and improved organ function. The beneficial effect of BMSCs was eliminated by macrophage depletion or pretreatment with antibodies specific for interleukin-10 (IL-10) or IL-10 receptor. Monocytes and/or macrophages from septic lungs made more IL-10 when prepared from mice treated with BMSCs versus untreated mice. Lipopolysaccharide (LPS)-stimulated macrophages produced more IL-10 when cultured with BMSCs, but this effect was eliminated if the BMSCs lacked the genes encoding Toll-like receptor 4, myeloid differentiation primary response gene-88, tumor necrosis factor (TNF) receptor-1a or cyclooxygenase-2. Our results suggest that BMSCs (activated by LPS or TNF-alpha) reprogram macrophages by releasing prostaglandin E(2) that acts on the macrophages through the prostaglandin EP2 and EP4 receptors. Because BMSCs have been successfully given to humans and can easily be cultured and might be used without human leukocyte antigen matching, we suggest that cultured, banked human BMSCs may be effective in treating sepsis in high-risk patient groups.
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PMID:Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production. 1949 65

Bilayered living-cell therapy has been shown in clinical trials to improve the rate of healing diabetic and venous leg ulcerations. However, literature is conflicted regarding the length of time living-cell therapy persists in acute and chronic wounds. An otherwise healthy 48-year-old man with sepsis from extensive lower-extremity wounds due to ecthyma gangrenosum was admitted to the hospital. Initial treatment consisted of surgical debridement, broad-spectrum antibiotics, and stabilization in the intensive care unit. After the patient was stabilized, three units of living-cell therapy meshed at a 3:1 ratio were applied to the wounds. Both wounds were healed after 20 weeks. Ten months post grafting, the patient returned with a recurrent ulcer in the area of graft placement. A biopsy of the wound for human leukocyte antigen revealed the presence of donor DNA from the bilayered living-cell therapy. This case suggests that bilayered living-cell therapy may persist for prolonged periods in patients without underlying skin disease or immunosuppression. Research to explicate the mode of action and optimal protocols for use of living-cell therapy is warranted.
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PMID:Persistence of bilayered living-cell therapy donor DNA 10 months after application: a case report. 2056 Feb 25

The immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) controls tryptophan metabolism and is induced by pro-inflammatory stimuli. We investigated whether immunostimulatory treatment with granulocyte-macrophage colony-stimulating factor (GM-CSF) influences IDO activity and tryptophan metabolism in sepsis. Thirty-six patients with severe sepsis/septic shock and sepsis-associated immunosuppression (assessed using monocytic human leukocyte antigen-DR (mHLA-DR) expression) were assessed in a controlled trial of GM-CSF or placebo treatment for 8 days. Using tandem mass spectrometry, levels of tryptophan, kynurenine, kynurenic acid, quinolinic acid, 5-hydroxytryptophan, serotonin, and estimated IDO activity were determined in a blinded fashion over a 9-day interval. At baseline, tryptophan and metabolite levels did not differ between the study groups. Although tryptophan levels were unchanged in both groups over the treatment interval (all p>0.8), IDO activity was markedly reduced after GM-CSF treatment (35.4 +/- 21.0 vs 21.6 +/-9.9 (baseline vs day 9), p = 0.02). IDO activity differed significantly between the 2 groups after therapy (p = 0.03). Metabolites downstream of IDO (kynurenine, quinolinic acid, kynurenic acid) were all induced in sepsis and declined in the GM-CSF group, but not in controls. Serotonin pathway metabolites remained unchanged in both groups (all p>0.15). Moreover, IDO activity correlated with procalcitonin (p< 0.0001, r = 0.56) and mHLA-DR levels (p = 0.005, r = -0.28) in the overall samples group. Thus, GM-CSF therapy is associated with decreased IDO activity and reduced kynurenine pathway catabolites in sepsis. This may be due to an improved antibacterial defence.
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PMID:Treatment with granulocyte-macrophage colony-stimulating factor is associated with reduced indoleamine 2,3-dioxygenase activity and kynurenine pathway catabolites in patients with severe sepsis and septic shock. 1995 38

The toxicity of chronic immunosuppressive agents required for organ transplant maintenance has prompted investigators to pursue approaches to induce immune tolerance. We developed an approach using a bioengineered mobilized cellular product enriched for hematopoietic stem cells (HSCs) and tolerogenic graft facilitating cells (FCs) combined with nonmyeloablative conditioning; this approach resulted in engraftment, durable chimerism, and tolerance induction in recipients with highly mismatched related and unrelated donors. Eight recipients of human leukocyte antigen (HLA)-mismatched kidney and FC/HSC transplants underwent conditioning with fludarabine, 200-centigray total body irradiation, and cyclophosphamide followed by posttransplant immunosuppression with tacrolimus and mycophenolate mofetil. Subjects ranged in age from 29 to 56 years. HLA match ranged from five of six loci with related donors to one of six loci with unrelated donors. The absolute neutrophil counts reached a nadir about 1 week after transplant, with recovery by 2 weeks. Multilineage chimerism at 1 month ranged from 6 to 100%. The conditioning was well tolerated, with outpatient management after postoperative day 2. Two subjects exhibited transient chimerism and were maintained on low-dose tacrolimus monotherapy. One subject developed viral sepsis 2 months after transplant and experienced renal artery thrombosis. Five subjects experienced durable chimerism, demonstrated immunocompetence and donor-specific tolerance by in vitro proliferative assays, and were successfully weaned off all immunosuppression 1 year after transplant. None of the recipients produced anti-donor antibody or exhibited engraftment syndrome or graft-versus-host disease. These results suggest that manipulation of a mobilized stem cell graft and nonmyeloablative conditioning represents a safe, practical, and reproducible means of inducing durable chimerism and donor-specific tolerance in solid organ transplant recipients.
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PMID:Chimerism and tolerance without GVHD or engraftment syndrome in HLA-mismatched combined kidney and hematopoietic stem cell transplantation. 2280 62


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