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

The appearance of the "streptococcal toxic shock-like syndrome" led to a growing interest in infections caused by Streptococcus pyogenes (group-A-streptococci). Since 1987 some 800 cases with a lethality of 20% or more were observed. Contrary to toxic scarlet fever the site of primary infection are the lower respiratory tract or soft tissue infections. Erythrogenic toxins and low molecular weight mitogens, inducing cytokines (IL-2, IL-3, IL-6, TNF-alpha, IFN-gamma) seem to be involved in the pathogenesis of these severe infections. Morphologically and culturally the strains isolated from cases of toxic shock-like syndrome cannot be differentiated from isolates of epidemic scarlet fever or sporadic cases. At the same time, when in Scandinavia an epidemic by S.pyogenes type 1 with many cases of toxic shock was observed, the same type caused a scarlet fever epidemic without complications in eastern Germany. Erythrogenic toxin type A or its toxoid, respectively, can be used for successful immunizations of rabbits. Another--antibacterial-immunization can be done with the M-protein of S.pyogenes, which is limited by its type-specificity. Streptococcal vaccination is required especially for developing countries with a high incidence of rheumatic fever. Infections due to Streptococcus agalactiae (group-B streptococci) are often underestimated though they have a first position in septicemia and meningitis of newborns. Taxonomy and nomenclature of streptococci are often changing; a list of the presently known species is presented in table I.
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PMID:[Epidemiology and pathogenesis of streptococcal infection]. 150 78

Interferon-gamma and other cytokines enhance macrophage (M phi) antimicrobial function and have been considered for therapeutic use in sepsis. Systemic sequelae of macrophage activation, however, are unclear. This study examined the effects of M phi activating cytokines (interferon-gamma [IFN-gamma] and interleukin-4 [IL-4]) and monoclonal antibodies directed against these cytokines in modulating the acute septic response. CFW/Swiss Webster mice (n = 345) received endotoxin (lipopolysaccharide [LPS]: 60 mg/kg body weight intraperitoneally) and were randomized to five treatment groups: IFN-gamma (10(4) units), IL-4 (10(4) units), IgG1 isotype antibody (TRFK5: 200 micrograms), anti-IFN-gamma (200 micrograms), or anti-IL-4 (200 micrograms) monoclonal antibodies (MAbs) given simultaneously or 2 hours after LPS. Animals were divided into two groups and studied for mortality or measurement of peritoneal M phi superoxide anion release (O2-), tumor necrosis factor (TNF), and IL-6 production 6 hours after administration of LPS +/- experimental regimens. Serum TNF and IL-6 also were assessed at 2 and 4 hours after LPS, respectively. Administration of LPS resulted in a 27% survival compared with 10% in the IFN-gamma and 13% in the IL-4 groups. Treatment with anti-IFN-gamma offered protection against LPS lethality (93%-100% survival, p less than 0.001 vs. other groups) when given either simultaneously or 2 hours after LPS. Anti-IFN-gamma also significantly decreased PM phi O-2 and TNF release. Thus anti-IFN-gamma may have an important role in the modulation of the acute septic response.
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PMID:Inhibition of macrophage-activating cytokines is beneficial in the acute septic response. 165 39

Monophosphoryl lipid A (MLA), a substructure of bacterial lipopolysaccharide (LPS), is being developed as a prophylactic for sepsis and septic shock. In the present study it was shown that MLA induced a rapid accumulation of IFN-gamma in mice that correlated with an in vivo priming of macrophages. Primed macrophages could be induced in vitro to synthesize nitric oxide, a key mediator of macrophage cytotoxicity. Due to its rapid clearance, MLA was not present in circulation at the time when IFN-gamma accumulated, suggesting that MLA could not synergize with IFN-gamma to systemically activate macrophages in vivo. MLA treatment tolerized mice against the IFN-gamma response--ie., treatment of mice with MLA on day 1 blocked LPS from inducing IFN-gamma on days 2-4. The significance of these results in relation to MLA's ability to enhance non-specific resistance and block LPS lethality in animals is discussed.
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PMID:A rationale for the prophylactic use of monophosphoryl lipid A in sepsis and septic shock. 173 86

A hyperdynamic sepsis model was set up in seven adult baboons to evaluate neutrophil-activating peptide-1/interleukin (IL)-8 (NAP-1/IL-8), IL-1 beta, IL-6, tumor necrosis factor-alpha (TNF alpha), and IFN-gamma in plasma. By continuous intravenous administration of 10(10) cfu/kg live Escherichia coli over 8 h with additional infusion therapy (less than or equal to 50 ml/kg/h), endotoxin plasma levels of 2.7-22.3 ng/ml were observed. In plasma the kinetics of NAP-1/IL-8 and IL-6 were similar to those of IL-1 at the end of the experiment (8 h) (peak median values, 34, 4197, and 230 ng/ml, respectively). Differences were greatest for IL-6. Monocyte activation during sepsis was confirmed by elevated plasma neopterin levels (91-139 mumol/mmol of creatine). Granulocyte activation was evident from both incipient neutropenia and the massive release of neutrophil elastase into the plasma as measured by a new immunoassay (peak level, 374 ng/ml). Thus, in primate bacteremia, early TNF release is followed by a concomitant increase of NAP-1/IL-8 with plasma kinetics similar to those of IL-6 and IL-1 and accompanied by massive activation of neutrophils.
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PMID:Plasma neutrophil-activating peptide-1/interleukin-8 and neutrophil elastase in a primate bacteremia model. 190 12

Various beneficial effects of calcium channel blockers on cell and organ function following endotoxic shock, organ ischemia, and reperfusion have been reported; however, it is not known whether these agents have any salutary or deleterious effects on immune responses after low-flow conditions. Therefore, the aim of this study was to determine (a) the effect of hemorrhage on lymphocyte IL-2, IL-3, IL-6, and IFN-gamma synthesis, and (b) whether diltiazem has any salutary or adverse effects on these parameters when administered following hemorrhage and resuscitation. To study this, C3H/HeN mice were bled to a mean blood pressure of 35 mm Hg, maintained at that level for 60 min, and resuscitated with shed blood plus twice that volume of Ringer's lactate. Immediately following resuscitation mice received either diltiazem (2400, 800, or 400 micrograms/kg body wt), or an equivalent volume of saline. The mice were sacrificed 24 hr later, splenic lymphocytes were obtained, and their capacity to produce lymphokines was assessed. The results indicated that in the vehicle-treated animals, hemorrhage significantly decreased (P less than 0.05) IL-2, IL-3, IL-6, and IFN-gamma synthesis by 82 +/- 19%, 64 +/- 28%, 71 +/- 11%, and 86 +/- 14%, respectively. However, diltiazem (400 but not 2400 micrograms/kg) treatment after hemorrhage restored lymphocyte capacity to produce IL-2, IL-3, IL-6, and IFN-gamma (P less than 0.05). Additional groups of animals were subjected to sepsis by cecal ligation and puncture 3 days following hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diltiazem restores IL-2, IL-3, IL-6, and IFN-gamma synthesis and decreases host susceptibility to sepsis following hemorrhage. 190 99

High levels of an acid-labile IFN-alpha have been demonstrated in the sera of patients with symptomatic HIV infection. IFNs have been shown to enhance the cytotoxic and antiproliferative actions of tumor necrosis factor (TNF), which is a potent mediator of inflammation and sepsis. We show that the acid-labile IFN-alpha present in AIDS sera can induce TNF synthesis and sensitize blood monocytes (BM) to endotoxin stimulation resulting in further synthesis of TNF in vitro. TNF production by BM from patients with HIV infections and normal controls was measured by a cytotoxicity assay on L929 cells using human TNF alpha as a standard. BM from AIDS patients spontaneously produce high levels of TNF and are hypersensitive to endotoxin stimulation, resulting in enhanced synthesis of TNF. In determining the mechanism involved, we demonstrated that treatment of normal BM with AIDS sera results in induction of TNF. Neutralization of the acid-labile IFN-alpha in AIDS sera with polyclonal anti-IFN-alpha antibodies results in diminution of TNF induction. In addition, pretreatment of normal BM with AIDS sera, IFN-alpha, or IFN-gamma renders the cells hypersensitive to endotoxin. Consequently, activation of the TNF system by the acid-labile IFN-alpha contributes to some of the physiological disturbances, such as the wasting syndrome, and to the pathophysiology of sepsis in AIDS patients.
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PMID:Endotoxin induction of tumor necrosis factor is enhanced by acid-labile interferon-alpha in acquired immunodeficiency syndrome. 250 43

The role of IFN-gamma in the regulation of host resistance of Staphylococcus aureus was studied using IFN-gamma receptor-deficient (IFN-gamma R-/-) mice in a model of S. aureus-induced septicemia and arthritis. IFN-gamma R-/- mice and wild-type controls were inoculated intravenously with a toxic shock syndrome toxin-1-producing S. aureus LS-1 strain. IFN-gamma R-/- mice displayed significantly more frequent and more severe arthritis compared with wild-type littermates (p < 0.01) throughout the course of infection. Notably, IFN-gamma R-/- mice developed severe sepsis with high mortality early after the inoculation with staphylococci. However, the mortality of wild-type mice became significantly higher at later stages of the disease compared with IFN-gamma R-/- mice (p < 0.05). This differential outcome of sepsis-related mortality was associated with deficiencies of bacterial elimination from blood and parenchymatous organs and correlated well to serum levels of IL-6 and spleen IL-1 beta and TNF-beta mRNA expression. Thus, bacterial growth and proinflammatory cytokines IL-1 beta, TNF-beta, and IL-6 were higher at the early stage of infection in IFN-gamma-/- mice but increased at the later stage in wild-type littermates. Our data indicate that the absence of IFN-gamma R leads to harmful as well as beneficial effects in S. aureus infection, depending on the stage of the disease and the localization of the infection.
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PMID:Impact of interferon-gamma receptor deficiency on experimental Staphylococcus aureus septicemia and arthritis. 749 61

Previous reports have suggested that the endotoxin-resistant C3H/HeJ strain of mouse is more susceptible to infection than is the endotoxin-sensitive parent strain, C3H/HeN, although they have never been compared in an i.v. model of sepsis. We therefore have used these mouse strains in an i.v. model of Gram-negative sepsis to compare their sensitivities to infection, their cytokine responses, and the levels of induction of the enzyme nitric oxide synthase assayed in their livers. By using i.v. infection with Escherichia coli we have found that both strains are approximately equally sensitive to this organism, despite the C3H/HeJ mice having a markedly attenuated TNF-alpha response. IFN-gamma levels after infection were identical in the two strains; the levels of nitric oxide synthase induced in their livers were about fourfold greater in the C3H/HeJ mice. This difference could not be explained by differences in bacterial load. These experiments suggest that factors other than TNF-alpha are important in determining outcome from Gram-negative sepsis and that TNF-alpha is not a major factor in the induction of hepatic nitric oxide synthase after infection in vivo.
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PMID:Differences in cytokine response and induction of nitric oxide synthase in endotoxin-resistant and endotoxin-sensitive mice after intravenous gram-negative infection. 768 16

Activation of the host defense system in a nonspecific way might provide tools to support failing antibiotic treatment in certain infectious diseases. The antimicrobial effect was investigated of liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (MTPPE) and interferon (IFN)-gamma and liposome-coencapsulated MTPPE and IFN-gamma on Klebsiella pneumoniae septicemia in mice. Prophylactic treatment of mice with five doses of liposomal MTPPE or IFN-gamma increased survival from 0 to 65%. Administration of MTPPE and IFN-gamma coencapsulated in liposome resulted in 100% survival. In vitro, peritoneal macrophages by themselves were stimulated by these agents but were unable to kill K. pneumoniae. However, production of both oxygen and nitrogen intermediates increased when immunomodulators were added to macrophages. These results indicate that effective prophylactic treatment of septicemia due to K. pneumoniae with coencapsulated MTPPE and IFN-gamma is not solely due to activation of the resident macrophages.
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PMID:Modulation of nonspecific antimicrobial resistance of mice to Klebsiella pneumoniae septicemia by liposome-encapsulated muramyl tripeptide phosphatidylethanolamine and interferon-gamma alone or combined. 784 75

Although studies indicate that polymicrobial sepsis produces marked depression in lymphocyte functions, it remains unclear whether this dysfunction is due to the chronic exposure of immune cells to endotoxin (ETX; a product of the gram-negative bacterial cell wall) at levels typically encountered in the septic state. The aim of this study, therefore, was to determine whether the changes in lymphokine release seen during polymicrobial sepsis are comparable to those observed with chronic ETX infusion. To assess this, splenocytes were harvested from C3H/HeN mice (ETX-sensitive) at 1 or 24 hr following cecal ligation and puncture (CLP; to induce polymicrobial sepsis), Sham CLP (Sham), or laparotomy followed by peritoneal implantation of a mini-osmotic pump which delivered either saline vehicle (Sal-pump) or ETX (ETX-pump; 0.025 micrograms lipopolysaccharide/25 g body wt/24 hr). Splenocytes were then stimulated with concanavalin A (2.5 micrograms/ml/48 hr) and their capacity to release interleukin (IL)-2, interferon (IFN)-gamma, IL-4, and IL-10 was determined by bioassay or ELISA. The results indicated that there were no changes in lymphokine release capacity at 1 hr after CLP or ETX-pump implantation. However, prolonged sepsis (i.e., at 24 hr) caused a marked suppression of IL-2 and IFN-gamma release (immune-enhancing lymphokines characteristic of Th1-cells), while enhancing the release of immunosuppressive Th2-cell products IL-4 and IL-10. Chronic exposure to ETX at a level comparable to that seen in CLP caused no depression in lymphokine (IL-2/IFN-gamma) release. This implies that a bacterial component other than ETX mediates the differential alterations observed in lymphokine release during prolonged polymicrobial sepsis.
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PMID:Polymicrobial sepsis but not low-dose endotoxin infusion causes decreased splenocyte IL-2/IFN-gamma release while increasing IL-4/IL-10 production. 801 14


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