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

Emerging concepts of sepsis suggest that the host response to an infectious stimulus results in some cases of uncontrolled release of inflammatory cytokines leading to signs of sepsis. Systemic inflammatory response syndrome (SIRS) has been suggested as a diagnosis when no etiologic organism can be found. Infection may account for up to 30% of cases of pre-term labor, and may either be clinically-evident or sub-clinical. Inflammatory cytokines can be detected in elevated concentrations in the amniotic fluid and plasma of women with pre-term labor, and human gestational tissues are potentially rich sources of inflammatory cytokines, as found in in vivo and in vitro studies. Also, maternal decidua and fetal membranes produce mRNA for inflammatory cytokines in the setting of infection-associated pre-term labor and normal term labor. Notably, anti-inflammatory cytokines, such as interleukin-10 (IL-10) do not appear to be present in substantial quantities in these pathophysiologic and physiologic conditions. Animal models indicate that pre-term labor can be stimulated by bacteria, bacterial cell wall products, and inflammatory cytokines such as IL-1 and tumor necrosis factor. These findings suggest that: (1) infectious stimuli may result in the liberation of inflammatory cytokines from gestational tissues leading inevitably to pre-term labor and delivery; (2) inhibition of this process may either be overcome or abrogated, and (3) the mechanisms regulating cytokine production in maternal and fetal tissues are disturbed. Thus, pre-term labor associated with sub-clinical infection may result in a dysregulated local inflammatory response, in which the maternal host response causes an 'intra-uterine inflammatory response syndrome' leading to pre-term labor and delivery.
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PMID:Pre-term labor: an intra-uterine inflammatory response syndrome? 943 Jul 41

We have previously shown that prophylactic administration of the liposome-encapsulated immunomodulating agents muramyl tripeptide phosphatidylethanolamine (MTPPE) and gamma interferon (IFN-gamma) results in strongly increased survival of mice from a normally lethal septicemia with Klebsiella pneumoniae. It was anticipated that the treatment acts on macrophages and nonspecifically augments host resistance to various infections. In the present study, we provide evidence for a key role for T cells in host defense potentiation by the liposomal immunomodulators toward K. pneumoniae septicemia. It is shown that both CD4 and CD8 cells are important in immunomodulation, most likely due to production of IFN-gamma. Depletion of circulating IFN-gamma resulted in strong reduction of the antimicrobial host defense activation. Administration of interleukin-10 resulted in decreased antimicrobial host defense activation by liposomal immunomodulators. Moreover, administration of liposomal immunomodulators was shown to induce predominantly T-helper type 1 (Th1) cell populations in the spleen. These findings indicate that immunomodulation with liposomal MTPPE and IFN-gamma favors Th1 and NK cell activation.
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PMID:Involvement of T cells in enhanced resistance to Klebsiella pneumoniae septicemia in mice treated with liposome-encapsulated muramyl tripeptide phosphatidylethanolamine or gamma interferon. 957 76

In normal conditions, alveolar macrophages (AMs) are the main cells that respond to bacteria that reach lower airways. However, if the microbial inoculum is too high or too virulent to be stopped by AM alone, these cells recruit polymorphonuclear neutrophils (PMN) into the alveoli from the vascular compartment. Cytokines, such as tumour necrosis factor-alpha (TNF-alpha), interleukin-1-beta (IL-beta), interleukin-6 (IL-6), and interleukin-8 (IL-8), secreted by the AM are able to attract PMN enhanced for phagocytosis, ready to destroy the invading pathogens. However, excessive cytokine production has deleterious effects, with a systemic inflammatory response (sepsis) that can lead to multiorganic failure and death. Other cytokines, such as interleukin-10 (IL-10) balance this response, attenuating several inflammatory mechanisms. The inflammatory lung response in pneumonia has been well studied in animals, and more recently in humans, using bronchoalveolar lavage to measure some inflammatory mediators (TNF-alpha, IL-1 beta, IL-6, IL-8). From these studies, it seems that: 1) the inflammatory response to pneumonia is compartmentalized for most cytokines (in contrast to adult respiratory distress syndrome (ARDS)), except for IL-6 which is a general marker of inflammation. On the other hand, C-reactive-protein is an acute-phase protein synthesized by the liver through the stimulus of IL-6 that may also be an easy-to-measure marker of inflammation that is directly related to IL-6; 2) some of these cytokines may be useful as prognostic indices; 3) there is no clear relationship between the local lung bacterial burden and the intensity of the inflammatory response; and 4) the administration of granulocyte colony-stimulating factor (G-CSF) is a promising therapeutic approach that is still under clinical investigation. In the future, it is probable that the therapeutic goal in severe pneumonia will be to find the exact point at which inflammation is beneficial but not deleterious. The measurement of the inflammatory response may serve for this purpose.
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PMID:Lung inflammatory response in pneumonia. 963 9

Infections that occur after intraabdominal surgery still cause considerable morbidity and mortality despite the administration of prophylactic antibiotics. Increasing the number of neutrophils may also be a prophylactic approach, and granulocyte colony-stimulating factor (G-CSF) has been found to be beneficial in different animal models of peritonitis and sepsis. It is the combination of G-CSF and antibiotics, however, that is clinically relevant. Treatment of mice with G-CSF that was started before cecal ligation and puncture and continued afterward with antibiotics improved survival, decreased splenic bacterial colony-forming units and serum tumor necrosis factor, and increased serum interleukin-10, compared with treatment with antibiotics alone or with saline. Compared with saline, antibiotics alone increased tumor necrosis factor and did not affect interleukin-10. Thus, G-CSF confers onto antibiotics beneficial antiinfectious and antiinflammatory properties. A prophylactic regimen combining G-CSF and antibiotics may help prevent severe infectious complications following intraabdominal surgery.
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PMID:Granulocyte colony-stimulating factor and antibiotics in the prophylaxis of a murine model of polymicrobial peritonitis and sepsis. 969 29

We evaluated the protective effect of interleukin-10 (IL-10) against murine gut-derived sepsis caused by Pseudomonas aeruginosa. Gut-derived sepsis was induced by administering cyclophosphamide and ampicillin while feeding P. aeruginosa to specific-pathogen-free mice. Treating mice with recombinant human IL-10 (rhIL-10) at 1.0 or 5.0 microg/mouse twice a day following the second cyclophosphamide administration significantly increased the survival rate compared to that of control mice treated with saline; however, treatment with rhIL-10 at 0.1 microg/mouse did not result in significant protection. Bacterial counts in the liver, spleen, and blood were all significantly lower in mice treated with rhIL-10 than in saline-treated control mice. Treatment with rhIL-10 significantly suppressed tumor necrosis factor alpha, interleukin-1beta, interleukin-6, and gamma interferon levels in the serum of mice following induction of gut-derived sepsis. We also studied the effect of IL-10 on leukocyte recovery after cyclophosphamide treatment of mice. Administration of rhIL-10 intraperitoneally at 1. 0 microg/mouse significantly accelerated the recovery of leukocytes in comparison with that of the group of saline-treated controls. These results indicate that IL-10 shows a protective effect against gut-derived P. aeruginosa sepsis. We suspect that the mechanism of this effect is that IL-10 regulates in vivo production of inflammatory cytokines. Furthermore, acceleration of leukocyte recovery by IL-10 after cyclophosphamide-induced depression may also play an important role in this protection.
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PMID:Effect of interleukin-10 on gut-derived sepsis caused by Pseudomonas aeruginosa in mice. 979 15

Pharmacological therapy of surgical disease often involves manipulating the physiologic balance between pro- and anti-inflammatory responses. Many agents target only one aspect of the inflammatory cascade. Originally identified as a protein elaborated by T-lymphocytes, IL-10 appears to globally inhibit cytokine production. The purpose of this manuscript is to examine the immunomodulatory and anti-inflammatory effects of interleukin-10 (IL-10) in an attempt to define the clinical utility of IL-10, both as a marker of and as a therapeutic strategy for intervention in inflammatory and immune-mediated diseases. IL-10 is elaborated from multiple sources and has diverse cellular effects to regulate immune and inflammatory responses. Accumulating evidence suggests that the anti-inflammatory influence of IL-10 observed at the cellular level may be manipulated to impact the immune and inflammatory-mediated responses associated with injury and sepsis, gastrointestinal and cardiovascular disease, and transplantation. In conclusion, IL-10 is an important mediator of immune and anti-inflammatory responses in surgical disease and, as such, has therapeutic promise as an immunomodulator and as an anti-inflammatory agent.
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PMID:Therapeutic implications of interleukin-10 in surgical disease. 984 Jun 44

Enhanced intestinal nitric oxide production observed during sepsis is thought to play a central role in lipopolysaccharide-induced intestinal damage. In contrast intestinal polyamines, both from endogenous and exogenous origin, are essential for the maintenance of mucosal integrity. Polyamines have been shown to inhibit lipopolysaccharide-induced nitric oxide release in vitro and have been claimed to exert additional antiinflammatory actions. In this study, the effect of the polyamine spermine on the release of the proinflammatory mediators nitric oxide and tumor necrosis factor-alpha by a murine macrophage cell line was investigated. Furthermore, we investigated whether oral spermine administration inhibits lipopolysaccharide-induced intestinal inducible nitric oxide synthase and nitrotyrosine expression and modulates the release of inflammatory mediators. Our results show that although spermine inhibited lipopolysaccharide-induced nitric oxide release in a murine macrophage cell line, no effect on tumor necrosis factor-alpha release was observed. In addition, oral spermine administration inhibited intestinal inducible nitric oxide synthase and nitrotyrosine expression suggesting a protective effect of spermine on lipopolysaccharide-induced intestinal damage. In parallel a decrease in serum levels of the proinflammatory mediators nitrate, nitrite, and interferon-gamma and an increase in the antiinflammatory cytokine interleukin-10 was observed, although tumor necrosis factor-alpha levels were unaffected. These results indicate that spermine inhibits lipopolysaccharide-induced nitric oxide release in vitro as well as in vivo. Further, intraluminally derived polyamines modulate the systemic immune response. It is concluded that oral spermine administration might have therapeutic perspectives for several disorders characterized by systemic inflammation and intestinal damage.
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PMID:Oral spermine administration inhibits nitric oxide-mediated intestinal damage and levels of systemic inflammatory mediators in a mouse endotoxin model. 1003 Jul 98

A protective effect of interleukin-10 (IL-10) against the development of lethal shock has been demonstrated in various animal models. In contrast, the immunosuppressant properties of this mediator have been minimally evaluated in low-mortality models of infections. The clinical, microbiological, and inflammatory effects of murine recombinant IL-10 (mrIL-10) therapy were evaluated in two models of peritonitis in rats, which differed in the degree of severity of peritoneal inflammation 3 days after inoculation of Escherichia coli and Bacteroides fragilis with or without Enterococcus faecalis. The severity of the disease remained unchanged compared to that in control animals. A dose-related decrease in the peritoneal phagocyte count was observed in the treated groups compared to the counts in control animals. The subsequent experiments were performed exclusively in the mixed gram-positive-gram negative model, which exhibits an intense and prolonged inflammatory response with similar criteria. The early effects of mrIL-10 (evaluated 6 h after inoculation), repeated injections of mrIL-10 (four doses injected from 0 to 9 h after bacterial challenge), and pretreatment (two doses injected 6 and 3 h before inoculation) were evaluated. The clinical and microbiological parameters remained unchanged in the treated animals. Decreases in the peritoneal phagocyte count and the peritoneal concentration of tumor necrosis factor were observed following repeated injections of mrIL-10. In summary, our data suggest that mrIL-10 does not worsen the manifestations of sepsis. However, these results need to be confirmed in clinical practice.
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PMID:Microbiological and inflammatory effects of murine recombinant interleukin-10 in two models of polymicrobial peritonitis in rats. 1008 89

During gram-negative sepsis, human monocytes are triggered to produce large quantities of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) in response to endotoxin (lipopolysaccharide [LPS]). Several studies have identified signal transduction pathways that are activated by LPS, including activation of nuclear factor-kappaB (NF-kappaB) and activation of mitogen-activated protein kinases (MAPKs), including ERK1 and ERK2, c-Jun N-terminal kinase, and p38. In this study, the relevance of ERK1 and ERK2 activation for LPS-induced TNF-alpha production by primary human monocytes has been addressed with PD-098059, which specifically blocks activation of MAPK kinase (MEK) by Raf-1. TNF-alpha levels in the monocyte culture supernatant, induced by 10 ng of LPS/ml, were reduced by PD-098059 (50 microM). In addition, PD-098059 also reduced TNF-alpha mRNA expression when cells were stimulated for 1 h with LPS. On the other hand, LPS-induced interleukin-10 (IL-10) levels in the monocyte supernatant were only slightly inhibited by PD-098059. Ro 09-2210, a recently identified MEK inhibitor, completely abrogated TNF-alpha levels at nanomolar concentrations. IL-10 levels also were strongly reduced. To show the efficacy of PD-098059 and Ro 09-2210, ERK1 and -2 activation was monitored by Western blotting with an antiserum that recognizes the phosphorylated (i.e., activated) forms of ERK1 and ERK2. Addition of LPS to human monocytes resulted in activation of both ERK1 and ERK2 in a time- and concentration (50% effective concentration between 1 and 10 ng of LPS/ml)-dependent manner. Activation of ERK2 was blocked by PD-098059 (50 microM), whereas ERK1 seemed to be less affected. Ro 09-2210 completely prevented LPS-induced ERK1 and ERK2 activation. LPS-induced p38 activation also was prevented by Ro 09-2210. These data further support the view that the ERK signal transduction pathway is causally involved in the synthesis of TNF-alpha by human monocytes stimulated with LPS.
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PMID:Lipopolysaccharide-induced tumor necrosis factor alpha production by human monocytes involves the raf-1/MEK1-MEK2/ERK1-ERK2 pathway. 1041 44

Bacterial translocation (BT) is a well-known insult during total parenteral nutrition (TPN) and a high incidence of morbidity has been reported in septic patients receiving TPN. Inflammatory cytokines were shown to play an important role in the pathogenesis of critical complications following sepsis. Previous studies have indicated that supplementation of TPN with glutamine is effective in preventing BT in animals, but its effectiveness in humans is unclear. The aim of this study was to determine the effectiveness of oral glutamine supplementation to patients receiving TPN in suppressing cytokine production of mesenteric blood mononuclear cells (M-MNC). Fifteen colorectal cancer patients were divided into 3 groups according to preoperative nutrition management. (1) TPN group: TPN with conventional glutamine-free amino acid solution. (2) Gln group: TPN with oral glutamine supplementation of 30 g/d. (3) CONTROL GROUP: oral intake of normal food. M-MNC were obtained immediately after laparotomy and tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) production of M-MNC was evaluated with or without lipopolysaccharide (LPS) stimulation. TNF-alpha and IL-10 production by LPS-stimulated M-MNC was increased in the TPN group and suppressed in the Gln group. In conclusion, oral glutamine supplementation to patients with TPN was shown to be effective for the prevention of M-MNC activation to avoid excessive production of cytokines.
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PMID:A clinical study of the effectiveness of oral glutamine supplementation during total parenteral nutrition: influence on mesenteric mononuclear cells. 1048 93


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