Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 2-month-old girl presented with enlarged head girth, generalized petechiae, anemia, coagulopathy and hepatosplenomegaly. Imaging studies showed a huge, dumbbell-shaped intracranial hemangioma located between the falx, and involving the supra- and infra-tentorium, extending through the posterior fontanel to involve the subgaleal area. A urine culture grew cytomegalovirus. Severe thrombocytopenia was refractory to a massive platelet transfusion, intravenous immunoglobulin and corticosteroid therapy. Hypertension, pulmonary hemorrhage and sepsis complicated the course. After establishing a diagnosis of Kasabach-Merritt syndrome, subcutaneous injections of alpha-interferon were given with an initial dose of 1 x 10(6) IU/m2 followed by 3 x 10(6) IU/m2 per day for 12.5 mo. Her platelet count rose gradually and became stable after 1.5 mo of interferon treatment. The intracranial hemangioma regressed remarkably and the hepatosplenomegaly was also resolved. The infant showed good growth and development, without obvious side-effects during the 23-month follow-up period. The treatment with recombinant alpha-interferon appeared to be effective in reversing thrombocytopenia associated with the patient's massive intracranial hemangioma.
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PMID:Recombinant alpha-interferon treatment of intracranial hemangioma and Kasabach-Merritt syndrome in an infant with cytomegalovirus. 761 60

Polyclonal antibodies were prepared to purified breast milk lactoferrin and used in an ELISA to measure plasma concentrations in investigations of various aspects of the inflammatory response. They were also used, in situ, to evaluate granulocyte lactoferrin content in disease states. The first series of studies addressed the putative role of lactoferrin in the pathogenesis of the hypoferremic, hyperferritinemic response to acute inflammation. Dissociation between the lactoferrin response and the iron related changes in rheumatoid arthritis and after alpha-interferon administration suggested that the relationship observed in acute and chronic bacterial infection may reflect coincidental effects of inflammatory cytokines. That lactoferrin does not mediate the inflammatory hypoferremic response was established by the finding that bone marrow transplant recipients, post-myeloablation, developed a hypoferremic response during septic episodes despite virtually undetectable plasma lactoferrin concentrations. The second series of investigations employed the plasma lactoferrin concentration as an index of granulocyte activation and function in a number of inflammatory conditions. Markedly increased initial plasma concentrations in acute pneumonia reflecting profound intravascular granulocyte activation were documented to predict sepsis related mortality. Plasma and granulocyte lactoferrin studies established that viral infection is associated with an acquired granulocyte lactoferrin deficiency. Plasma measurements indicated that asthmatics, even when clinically asymptomatic, have evidence of persistent granulocyte activation.
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PMID:Lactoferrin and the inflammatory response. 776 25

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

The objective of this study was to determine nitric oxide (NO) and superoxide anion release (O-2) by neutrophils (PMNs) in the septic multiple organ dysfunction syndrome (MODS) and to compare them with the response of normal cells to lipopolysaccharide (LPS) and cytokines. NO production was measured by the release of nitrites in the medium, its maximal production rate by a modified oxyhemoglobin assay and O-2 by standard methods. Normal cells were incubated with LPS, gamma interferon (IFN-gamma), or tumor necrosis factor (TNF-alpha) alone or in combination. Results showed that PMN release of both NO and O-2 was reduced in septic samples; in contrast, an association of LPS, IFN-gamma, and TNF-alpha promoted maximal NO release by normal cells (40-50%). We conclude that while interaction of normal PMNs with cytokines increases NO and O-2 release, progression of sepsis to a multiple organ dysfunction impairs these responses in both functions.
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PMID:Decreased production of nitric oxide by human neutrophils during septic multiple organ dysfunction syndrome. Comparison with endotoxin and cytokine effects on normal cells. 807 Sep

Interleukin-2 (IL-2) and alpha-interferon have each shown antitumor activity in patients with disseminated malignant melanoma. Because animal studies suggest enhanced activity for the combination over each agent used alone, this trial using a relatively low-dose outpatient regimen was undertaken. IL-2 at a dose of 2 x 10(6) U/m2/day (Roche units) was given by continuous intravenous infusion for 4 days a week with interferon-alpha-2a at a dose of 6 x 10(6) U/m2/day given by s.c. or i.m. injection on days 1 and 4 of each treatment week. One cycle consisted of 4 consecutive weeks of treatment followed by a 2-week rest period. Fourteen patients were entered in this study. No complete or partial responses were seen. One patient required dose reduction because of grade 3 diarrhea and two patients had interruption of treatment because of central-line-related sepsis. Fatigue was common in all patients. This low-dose combination regimen of IL-2 and alpha-interferon does not appear to be better than the single agents used alone in optimal dosage.
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PMID:A phase II trial of concomitant human interleukin-2 and interferon-alpha-2a in patients with disseminated malignant melanoma. 831 96

During severe sepsis syndromes, almost every gene coding for cytokines may be activated. The primary purpose of this activation is to defend the organism against infection, but sometimes these inflammatory mediators go out of control. The reasons why this may occur is unclear because the regulation of cytokines production is still poorly understood. Metabolic effects, production of endothelial adhesion molecules and triggering of neutrophils are some important consequences of cytokine overstimulation which may lead to the clinical picture of septic shock. The major cytokines involved in septic shock are tumor necrosis factor alpha (TNF) and interleukin-1 (IL-1). Both may induce lethal shock in experimental models. The effects of these 2 cytokines are difficult to differentiate from one another because they share many similar biological effects, one can induce the synthesis of the other, and they are strikingly synergistic with each other. gamma-interferon may amplify the inflammatory response by stimulating the cells of monocytic lineage and by increasing TNF-receptor expression, thus participating in the pathogenesis of the septic syndrome. The role of other cytokines is still poorly known. Clinical studies with anti-TNF monoclonal antibodies or with an IL-1 receptor antagonist are under way.
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PMID:[Cytokines and severe sepsis]. 834 26

The case of a 34-year-old female is reported, who has suffered from recurring condylomata acuminata of the anogenital region since she was 16. In the further course of the disease multiple Buschke-Loewenstein tumors developed, and finally an invasively growing, highly differentiated, keratinizing squamous cell carcinoma. The course of the disease was complicated by severe septicemia. In the framework of multimodal therapy, laser resection was the preferred method of surgical intervention. A systemic or local interferon treatment has only a prophylactic character in this stage of the disease.
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PMID:[Monstrous Buschke-Loewenstein tumor (condylomata acuminata gigantea) with transition to invasive squamous epithelial cancer]. 835 63

Cytokines are suspected of playing an important role in the pathophysiology of septic shock. This study was undertaken to determine whether tumor necrosis factor alpha (TNF-alpha) induces the production of other cytokines and mediates mortality in a neonatal rat model of sepsis caused by group B streptococci (GBS). We have measured TNF-alpha, interleukin-1 alpha (IL-1 alpha), interleukin-6 (IL-6), and gamma interferon (IFN-gamma) levels in neonatal rats infected with different strains (H738, 259, and 90) and doses (1 50% lethal dose [LD50] and 5 90% lethal doses [LD90]) of type III GBS. TNF-alpha and IL-6 were detected by the L929 cytotoxicity and the B9 proliferation assays, respectively, in serial plasma samples. IL-1 alpha and IFN-gamma were measured in spleen homogenates by enzyme-linked immunosorbent assay kits by using antibodies raised against the corresponding mouse cytokines. Plasma TNF-alpha levels significantly rose above baseline values within 12 h after intraperitoneal challenge with 5 LD90 of GBS strain H738, corresponding to 3 x 10(3) CFU. A mean peak TNF-alpha concentration of 232 +/- 124 U/ml was reached at 20 h. Peak IL-1 alpha and IL-6 levels of 766 +/- 404 U/g and 1,033 +/- 520 U/ml, respectively, were reached at 24 h after bacterial challenge. Maximal spleen concentrations of IFN-gamma (449 +/- 283 U/g) were measured at 36 h. Concentrations of TNF-alpha, but not other cytokines, remained significantly elevated at 72 h, a time when mortality approached 100%. Significant correlations were found between concentrations of each of the cytokines tested and the logs of CFU concentrations in the blood. In order to ascertain whether TNF-alpha influenced the production of other cytokines, rat pups received two injections of anti-murine TNF-alpha or normal rabbit serum at 2 h before and at 26 h after challenge with live GBS. Plasma TNF-alpha bioactivity was undetectable in anti-TNF-alpha-treated animals, while IL-6 and IFN-gamma, but not IL-1 alpha, levels were significantly reduced, compared with normal serum controls. Rat pups pretreated with anti-TNF-alpha serum and infected with 1 and 5 LD90 of strains H738 and 259 showed enhanced early (48 to 72 h) survival. However, by 96 h this protection was no longer apparent.
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PMID:Cytokine appearance and effects of anti-tumor necrosis factor alpha antibodies in a neonatal rat model of group B streptococcal infection. 841 44

Injury has been hypothesized to cause inflammation through systemic release of lipopolysaccharide and pro-inflammatory cytokines, but this has proved difficult to demonstrate in humans. We looked for evidence of an inflammatory pattern of cytokine gene expression by peripheral blood mononuclear cells (PBM) in six polytraumatized patients (ISS = 25 +/- 8) upon ER admission, and in six matched healthy controls. PBM tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-4, IL-6, IL-10, and interferon (IFN)-gamma message was assessed by semi-quantitative reverse-transcription polymerase chain reaction. No increase in expression of any of the pro-inflammatory cytokines (tumor necrosis factor-alpha, IL-1 beta, or IL-6) was found after trauma, and IFN-gamma tended to decrease. Of the immunosuppressive cytokines, IL-10 expression increased 5-fold (p < .05) but no change in IL-4 was discerned. This pattern is fundamentally different from the cytokine expression patterns expected with sepsis or exposure to lipopolysaccharide. These findings are inconsistent with the occurrence of systemic endotoxemia and subsequent global immunocyte activation early after trauma.
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PMID:Human peripheral mononuclear cells do not show proinflammatory patterns of cytokine transcription in early trauma: a preliminary report. 856 51


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