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)

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.
 ...
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.
 ...
PMID:[Cytokines and severe sepsis]. 834 26

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.
 ...
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.
 ...
PMID:Human peripheral mononuclear cells do not show proinflammatory patterns of cytokine transcription in early trauma: a preliminary report. 856 51

Cryofiltration apheresis (CA) is a specific therapy for treatment of patients with cryoglobulinemia. We evaluated the safety and efficacy of CA in patients with mixed cryoglobulinemia associated with hepatitis C. As reported previously, the Cryoglobulin Filter comprises a membrane module inside a refrigeration unit on-line with a Spectra Apheresis System (COBE, Denver, CO). The efficacy of cryofiltration was measured by comparing the sieving coefficient of cryoprecipitable proteins (CPP) to that of albumin and comparing the systemic CPP concentration ratio post to pre treatment. Five patients were enrolled in this study, and a minimum of 10 procedures were performed for each patient. The risk for hepatitis C was multiple blood transfusions, intravenous drug abuse, immunosuppressive therapy, or renal transplantation. Four patients had Type II mixed cryoglobulinemia, and one patient had Type III. Four patients had chronic renal failure; one with liver cirrhosis received alpha interferon along with CA. One patient had no response to conventional plasma exchange and immunosuppressive therapy secondary to repeated infections and sepsis; CA was the only viable therapy for this patient. The maximum CPP concentration before therapy ranged from 1,440 to 7,440 micrograms/ml. The plasma CPP sieving coefficient at 1 L filtrate ranged from 0.25 to 0.74 (average +/- SE, 0.51 +/- 0.19; n = 39). The sieving coefficient for albumin was 1 (n = 50). The systemic CPP ratio post to pre treatment ranged from 0.28 to 0.83 (average +/- SE, 0.59 +/- 0.20; n = 37). No adverse effects specific to CA were observed. The CA was safe and effective and possibly the only choice of therapy in patients with cryoglobulinemic hepatitis C who have no response to plasma exchange and immunosuppressive therapy.
 ...
PMID:Cryofiltration apheresis for treatment of cryoglobulinemia associated with hepatitis C. 857 15

The existence of interleukin-12-mediated innate immune responses to group B streptococci (GBS) was tested by examining T-lymphocyte-independent gamma interferon (IFN) production in cultured splenocytes from severe combined immunodeficiency mice. Splenocytes were cultured with killed or living GBS for 48 h, and then IFN was measured by enzyme-linked immunosorbent assay. Type III GBS as well as other extracellular bacterial agents of neonatal sepsis (staphylococci and enterococci) induced IFN production, which was enhanced by interleukin-2 and was inhibited by neutralizing antibodies to tumor necrosis factor alpha and to mouse interleukin-12. Interleukin-12 bioactivity was present in conditioned medium from GBS-treated adherent macrophages. Adherent peritoneal macrophages and bone marrow-derived natural killer cells from severe combined immunodeficiency mice cultured separately with GBS did not produce IFN, whereas cocultures did produce IFN. Functional macrophage activation was evident by nitric oxide production in GBS-treated splenocyte cultures. The results show that extracellular pathogens such as GBS, similarly to intracellular microbes, induce macrophage interleukin-12 and tumor necrosis factor alpha, which promote natural killer cell secretion of IFN, which then enhances innate phagocyte resistance mechanisms.
 ...
PMID:Interleukin-12 and tumor necrosis factor alpha mediate innate production of gamma interferon by group B Streptococcus-treated splenocytes of severe combined immunodeficiency mice. 860 95

Certain cytokines, particularly gamma-interferon (IFN) and interleukin (IL)-2 associated with TH1 cell function, have been shown to play a role in allograft rejection. One paradigm for long-term allograft acceptance involves TH2 cytokine predominance (IL-4 and IL-10). We describe two renal allograft recipients for whom immunosuppression was discontinued due to serious sepsis and who maintained stable renal function over 2-6 months without immunosuppression. During this time, there were higher levels of both IFN-gamma and IL-10 in the peripheral blood than in stable control kidney transplant recipients on immunosuppression. In one of the patients, levels of IL-10 fell, while those of IFN-gamma remained persistently elevated. This was associated with biopsy-proven rejection. Although peripheral blood cytokine levels may not reflect intragraft events, these data are consistent with an allograft protective role for IL-10 offsetting that of IFN-gamma in both patients off immunosuppression.
 ...
PMID:Association of interleukin-10 with rejection-sparing effect in septic kidney transplant recipients. 862 96

Thirty-four patients with advanced malignant melanoma were treated with recombinant alpha-interferon (IFN) and chemotherapy consisting of carboplatin, vinblastine, and bleomycin (CVB). CVB was given for four cycles and IFN for 1 year or until progression. Of the 34 analyzed patients, 17 (50%) achieved an objective response, including two complete (6%) and 15 partial responses (44%). Responses were noted in cutaneous, lymph node, and pulmonary sites, with a median time to disease progression of 5 months (range, 3-20 months). The median survival from onset of therapy was 8 months (range, 1-22 months) for the 34 patients. Ninety-four percent of the patients experienced flu-like symptoms and 82% fatigue or weakness. Leukopenia grade 3-4 was observed in four patients (12%). There were two toxicity-related deaths (6%); one from bleomycin-induced pneumonitis and one from neutropenic sepsis. It is concluded that the addition of IFN to CVB regimen, in this study, showed no apparent advantage on response rates, disease-free interval, or survival. The observed treatment-related mortality was unacceptably high. IFN administered as maintenance therapy following CVB conferred no survival benefit.
 ...
PMID:Recombinant interferon ALFA-2A in combination with carboplatin, vinblastine, and bleomycin in the treatment of advanced malignant melanoma. 863 45

The aim of this study was to assess the role of gamma interferon (IFN-gamma) in a neonatal mouse model of group B streptococcal (GBS) sepsis. IFN-gamma was produced by spleen cells at 24, 48, and 72 h after GBS challenge. Treatment with anti-IFN-gamma at 6 h before challenge totally abrogated the IFN-gamma response but did not affect survival. Subcutaneous administration of recombinant IFN-gamma (2,500 IU per pup) at 18 h after challenge resulted in increased survival time and reduced blood colony counts at 48 and 72 h. In vitro preincubation of neonatal whole blood with IFN-gamma before the addition of GBS resulted in significant restriction of bacterial growth. These data indicate that administration of recombinant IFN-gamma can partially restore impaired host defenses against GBS in neonatal mice. This cytokine may be useful for the treatment of neonatal infections.
 ...
PMID:Role of gamma interferon in a neonatal mouse model of group B streptococcal disease. 875 17

Platelet-activating factor (PAF) was tested for its ability to alter yields of human interferon (IFN) produced from peripheral blood mononuclear cells (PBMC). Using different concentrations of phytohemagglutinin (PHA) we could not demonstrate a consistent effect of PAF at any concentration tested on the yield of IFN-gamma. Similarly, although PAF was associated with a slight enhancement of IFN-gamma yields when PBMC were induced by interleukin-2 (IL-2), the results were not statistically significant. No effect was observed on the accumulation of human IFN-gamma mRNA induced by PHA. Furthermore, PAF did not enhance yields of IFN-gamma when the cells were induced by poly I:poly C. We conclude that although PAF may have a role in sepsis, it is not likely that this is in any way related to its ability to significantly alter the yield of interferons.
 ...
PMID:Platelet-activating factor and the production of human interferon-gamma. 905 17


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>