Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We measured the plasma levels of anti-inflammatory cytokines, including interleukin 1 receptor antagonist (IL-1ra), IL-4 and IL-10; inflammatory cytokines, including IL-2, IL-6, IL-8 and tumor necrosis factor receptor I and II (TNFR I and TNFR II); and endotoxin in 11 patients with septic shock associated with gram-negative bacteria and 12 patients with sepsis not associated with shock. The plasma levels of IL-1ra and IL-10 were elevated in the septic shock group compared with the sepsis group. TNFR I and TNFR II levels tend to be higher in the septic shock group. The plasma level of TRNF-alpha was significantly correlated with levels of IL-1ra, IL-4, IL-10, TNFR I, and TNFR II. The elevated levels of the anti-inflammatory cytokines, TNFR I, and TNFR II, appeared to reflect an attempt to suppress the shock syndrome.
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PMID:Anti-inflammatory cytokine levels in patients with septic shock. 943 13

Epinephrine has been found to inhibit the production of the proinflammatory cytokine tumor necrosis factor (TNF)-alpha and to enhance the production of anti-inflammatory cytokine interleukin (IL)-10. To determine the effect of epinephrine on IL-1 beta production, the following experiments were performed: 1) blood obtained from subjects at 4-21 h after the start of a continuous infusion of epinephrine (30 ng.kg-1.min-1) produced less IL-1 beta after ex vivo stimulation with lipopolysaccharide (LPS), compared with blood drawn from subjects infused with saline; 2) in whole blood in vitro, epinephrine caused a dose-dependent decrease in LPS-induced IL-1 beta production, which was likely mediated via adrenergic receptors; and 3) inhibition of TNF and enhancement of IL-10 both contributed to epinephrine-induced inhibition of IL-1 beta production. Epinephrine, either endogenously produced or administered as a component of sepsis treatment, may attenuate excessive activity of proinflammatory cytokines early in the course of systemic infection.
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PMID:Epinephrine inhibits endotoxin-induced IL-1 beta production: roles of tumor necrosis factor-alpha and IL-10. 943 41

Systemic bacterial lipopolysaccharides (LPS) induce inflammatory responses characteristic of sepsis. Instillation of LPS into rat bladder produces a localized inflammatory response similar to that seen in urinary tract infections (UTIs). Four hours after intravesical instillation of LPS, neutrophils infiltrate into the bladder, and mRNA for inducible nitric oxide synthase (iNOS) and the cytokines, interleukin (IL)-6 and IL-10, is detected in rat bladder but not in the kidney. Induction of iNOS protein is inferred because urinary nitrate and cGMP levels are increased 4 hr after LPS intravesical instillation and remain elevated for at least 24 hr. When LPS is injected intraperitoneally, iNOS and IL-6 mRNA are induced both in the bladder and in the kidney. These data are consistent with the effects of intravesical instillation of LPS remaining localized, iNOS activity increases in both particulate and soluble bladder fractions when measured 4 hr after intravesical instillation of LPS. The magnitude of these increases in iNOS activity in the bladder is not as great as when LPS is injected intraperitoneally. Intravesical instillation of LPS induces no increase in lung or kidney NOS activity. The localized inflammatory response produced by intravesical instillation of LPS demonstrates the importance of LPS as a mediator of the host response in UTIs and supports the use of urinary measurements of nitrate and cGMP in humans as indicative of the localized induction of iNOS in UTIs.
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PMID:Bladder instillation and intraperitoneal injection of Escherichia coli lipopolysaccharide up-regulate cytokines and iNOS in rat urinary bladder. 949 84

We evaluated the effect of C1 inhibitor (C1-inh), an inhibitor of the classical pathway of complement and the contact system, on the physiologic and inflammatory response in baboons suffering from lethal Escherichia coli sepsis. Five animals pretreated with 500 U/kg C1-inh (treatment group; n = 5), followed by a 9-h continuous infusion of 200 U/kg C1-inh subsequent to bacterial challenge, were compared with five controls receiving E. coli alone. Of the treatment group, one animal survived and another lived beyond 48 h, whereas all control animals died within 27 h. In four of five treated animals, less severe pathology was observed in various target organs. C1-inh administration did not prevent the hemodynamic or hematologic changes observed upon E. coli infusion. The activation of fibrinolysis and the development of disseminated intravascular coagulation were essentially unaffected by C1-inh. However, C1-inh supplementation significantly reduced decreases in plasma levels of factor XII and prekallikrein and abrogated the systemic appearance of C4b/c, indicating substantial inhibition of activation of the contact system and the classical complement pathway, respectively. Furthermore, treated animals displayed a reduced elaboration of various cytokines including TNF, IL-10, IL-6, and IL-8. Thus, the administration of C1-inh may have a beneficial but modest effect on the clinical course and outcome of severe sepsis in nonhuman primates. We suggest that activated complement and/or contact system proteases may, at least in part, contribute to the attendant manifestations of septic shock through an augmentation of the cytokine response.
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PMID:Effect of C1 inhibitor on inflammatory and physiologic response patterns in primates suffering from lethal septic shock. 955 6

Ex vivo cytokine production by circulating lymphocytes and monocytes is reduced in patients with infectious or noninfectious systemic inflammatory response syndrome. Very few studies have addressed the reactivity of polymorphonuclear cells (PMN). To analyze further the relative contribution of systemic inflammatory response syndrome alone or in combination with infection we studied the interleukin-8 (IL-8) production by PMN isolated from patients who had undergone cardiac surgery with cardiopulmonary bypass (CPB) and patients with sepsis. Cells were activated with either lipopolysaccharide (LPS) or heat-killed streptococci. Compared with healthy controls, the release of IL-8 by PMN in both groups of patients was significantly reduced whether activated by LPS, independently of its concentration and origin, or by heat-killed streptococci. These observations suggest that stressful conditions related to inflammation, independently of infection, rapidly dampened the reactivity of circulating PMN. We investigated whether the observed diminished reactivity of PMN might reflect an endotoxin tolerance phenomenon. Our in vitro experiments with PMN from healthy controls indicated that PMN could not be rendered tolerant stricto sensu. However, our data suggested that LPS-induced mediators such as IL-10 may be responsible for the observed anergy in patients.
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PMID:Reduced ex vivo interleukin-8 production by neutrophils in septic and nonseptic systemic inflammatory response syndrome. 955 3

An in vitro model for the study of sepsis mediators was used to investigate the effects of two different lipopolysaccharides (LPS), a smooth (LPS-S) and a rough (LPS-R) type, on the release of chemokines (IL-8 and MIP-1 alpha) and cytokines (TNF alpha, IL-1 beta, IL-1ra and IL-10) from human whole blood samples. TNF alpha level increased significantly vs. control, at 4 h and 8 h after the challenge with smooth and rough type of LPS respectively. Concentrations of the two chemokines studied, IL-8 and MIP-1 alpha, were significantly elevated following stimulation by both LPS, and reached concentrations significantly different from controls at 4, 8 and 24 h. After 24 h of incubation both LPS produced a significant IL-10 increase, although such change was more substantial with the rough type. Present data suggest an early and maintained release of chemokines regardless of the type of LPS used and often in absence of a significant increase in primary pro-inflammatory cytokines.
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PMID:Kinetics of IL-8, MIP-1 alpha, TNF alpha, IL-1 beta, IL-1ra and IL-10 in human whole blood samples triggered by smooth and rough LPS. 957 36

Lack of IL-4 has been shown to be protective in some experimental models of infectious diseases in mice such as cutaneous leishmaniasis. At the same time IL-4, together with other Th2 cytokines, including IL-10 and IL-13, is known as an anti-inflammatory cytokine with the potential to down-regulate proinflammatory cytokine production. To investigate the role of IL-4 in experimental Staphylococcus aureus-induced and T lymphocyte-mediated arthritis, IL-4-deficient C57BL/6 mice (IL-4(-/-)) and their congenic controls (IL-4(+/+)) were inoculated with a toxic shock syndrome toxin-1-producing S. aureus strain. In IL-4(+/+) mice, arthritis peaked 14 days after bacterial inoculation, whereas, at that time, IL-4(-/-) mice displayed significantly less frequent (p < 0.05) joint inflammation. Paralleling lower frequency of arthritis, IL-4-deficient mice showed a decreased bacterial burden in joints (p = 0.014) and kidneys (p = 0.029), as well as lower infection-triggered weight decrease and mortality. In vitro, IL-4 inhibited intracellular killing of S. aureus in infected macrophages, without affecting phagocytosis. This finding may explain the enhanced staphylococcal clearance observed in IL-4(-/-) mice in vivo. Our results suggest that IL-4 and IL-4-dependent Th2 responses promote septic arthritis and sepsis-related mortality by inhibition of bacterial clearance during S. aureus infection.
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PMID:Staphylococcus aureus-induced septic arthritis and septic death is decreased in IL-4-deficient mice: role of IL-4 as promoter for bacterial growth. 959 Feb 59

Macrophages can respond to a variety of infectious and/or inflammatory stimuli by secreting an array of proinflammatory cytokines, the overproduction of which can result in shock or even death. In this report, we demonstrate that ligation of macrophage Fcgamma receptors (FcgammaR) can lead to a reversal of macrophage proinflammatory responses by inducing an upregulation of interleukin (IL)-10, with a reciprocal inhibition of IL-12 production. IL-10 upregulation was specific to FcgammaR ligation, since the ligation of the Mac-1 receptor did not alter IL-10 production. The identification of the specific FcgammaR subtype responsible for IL-10 upregulation was determined in gene knockout mice. Macrophages from mice lacking the FcR gamma chain, which is required for assembly and signaling by FcgammaRI and FcgammaRIII, failed to upregulate IL-10 in response to immune complexes. However, mice lacking either the FcgammaRII or the FcgammaRIII were fully capable of upregulating IL-10 production, implicating FcgammaRI in this process. The biological consequences of FcgammaRI ligation were determined in both in vitro and in vivo models of inflammation and sepsis. In all of the models tested, the ligation of FcgammaR promoted the production of IL-10 and inhibited the secretion of IL-12. This reciprocal alteration in the pattern of macrophage cytokine production illustrates a potentially important role for FcgammaR-mediated clearance in suppressing macrophage proinflammatory responses.
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PMID:Reversal of proinflammatory responses by ligating the macrophage Fcgamma receptor type I. 965 99

Sepsis remains a major cause of mortality in surgical intensive care units. Patients who survive the initial shock phase but die weeks later from multiple organ dysfunction still are a challenge to basic and clinical research. We addressed whether fulminant sepsis results in rapid changes (24 h) in the cellular capacity to produce cytokines in whole blood of septic patients on further stimulation after the initial systemic inflammatory response. Interleukin (IL)-6 plasma concentrations from 279 pg/mL to 5979 pg/mL confirmed the presence of a systemic inflammatory response. Anti-inflammatory IL-10 concentrations up to 275 pg/mL were detected, but there was no biologically active tumor necrosis factor-alpha (TNFalpha) detectable (by bioassay) at the time of investigation. On stimulation with Escherichia coli ex vivo, pro-inflammatory TNFalpha (130 pg/mL), IL-6 (4061 pg/mL), and anti-inflammatory IL-10 (711 pg/mL) production were markedly depressed in all patients compared with controls (2339 pg/mL, 50,319 pg/mL, and 9654 pg/mL, respectively). Septic shock resulted in early depression of the capacity for pro- and anti-inflammatory cytokine production. Monitoring of this effect, including its relationship to outcome, may offer a target variable for therapeutic efforts to maintain or restore adequate immune reactions to improve survival.
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PMID:Depression of tumor necrosis factor-alpha, interleukin-6, and interleukin-10 production: a reaction to the initial systemic hyperactivation in septic shock. 965 91

The objective of the investigation was to evaluate the possible use of selected cytokines and cytokine receptors in the early diagnosis of postoperative intraabdominal sepsis. The investigation was focused on the dynamics of plasma levels of tumour necrotizing factor-alfa (TNFalfa), interleukin (IL)-1beta, IL-2, IL-6, IL-8, IL-10, soluble receptors IL-2 and IL-6 (sIL-2R and sIL-6R) and the receptor antagonist IL-1 (IL-1ra). The investigated parameters were tested on model operations (resection of large bowel and resection of pancreas). These two groups were compared with values recorded in patients with sepsis and with healthy subjects. Based on the assembled results the authors recommend to use for postoperative investigations the first 48 hours and to follow up the following parameters: IL-6, IL-ra or sIL-2R. During the first 48 hours these indicators differentiate sufficiently specifically incipient sepsis from an uncomplicated postoperative condition. During the subsequent period, i.e. more than 48 hours after surgery, it is useful to include in the examination pattern also some acute stage proteins (C reactive protein, alfa1-antitrypsin and haptalobin) which differentiate sepsis between the 3rd and 5th day after surgery.
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PMID:[The significance of cytokines in the early diagnosis of postoperative intraabdominal sepsis]. 965 57


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