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)

Recombinant human granulocyte/macrophage colony-stimulating factor (rhGM-CSF) was administered to a patient with multiple myeloma (IgA, stage IIA) who had a chemotherapy-induced bone marrow aplasia with granulocytopenia complicated by severe pneumonia and septicemia. The rhGM-CSF was given as i.v. infusions, 300-400 micrograms daily, for three weeks. The patient responded both hematologically and clinically with improved granulocyte counts and clearance of massive pulmonary infiltrates. We also observed a partial remission of the myeloma with decreasing s-IgA levels and reduced plasma cell infiltration of the bone marrow during a period of up to four months after the rhGM-CSF treatment. Immunological studies performed during and after cytokine administration showed an increase in serum interleukin-2 (IL-2) levels and HLA-DR positive T-lymphocytes indicating an activation of the immune system. It is suggested that rhGM-CSF induced immunological changes which may have contributed to the partial regression of the myeloma.
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PMID:Increase of serum interleukin-2 and regression of myeloma after rhGM-CSF treatment of drug induced bone marrow aplasia. 193 5

Haemopoietic growth factors (HGFs) are being administered to patients with neutropenic fever; however, little is known about the endogenous HGF response in these patients. Specific assays were used to study four HGFs, granulocyte (G-) CSF, granulocyte-macrophage (GM-) CSF, macrophage (M-) CSF and interleukin (IL-) 6 levels in the blood of patients with neutropenic fever (46 episodes). For comparison, levels were also measured in three control populations: normals (20), afebrile neutropenic (14), and bacteraemic but not neutropenic patients (20). In febrile patients, levels of G-CSF (median, range) (0.46, < 0.10-142 ng/ml). IL-6 (0.054, 0.005-24.3 ng/ml) and M-CSF (18.5, 9.9-79.1 ng/ml) were elevated compared with afebrile subjects (< 0.10, < 0.10-1.62 ng/ml). (0.008, 0.002-0.024 ng/ml) and (6.45, < 5.0-31.3 ng/ml) respectively. GM-CSF was not elevated (< 0.02, < 0.02-8.0 ng/ml) compared with afebrile subjects (0.021, < 0.02-0.20 ng/ml). Variables significantly associated (P < 0.05) with elevated cytokine levels were determined by multiple regression analyses. Factors associated with G-CSF elevation were fever, neutropenia, pathogen type and raised bilirubin and creatinine. In contrast, neutropenia was not associated with IL-6 elevation although there was an association between IL-6 elevation and fever, Gram-negative and fungal infections and raised creatinine and bilirubin. M-CSF elevation was associated with fever, renal impairment and known pathogen. Elevated G-CSF and IL-6 levels normalized rapidly (hours-days) with the resolution of infection, whereas M-CSF concentrations remained elevated for up to 10 d. Cytokine levels remained elevated in septic neutropenic patients who did not recover. In summary, G-CSF, IL-6 and M-CSF levels were significantly elevated in sepsis. In contrast, GM-CSF levels were not elevated. These studies should assist the development of therapeutic strategies using HGFs in the treatment of sepsis.
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PMID:Endogenous haemopoietic growth factors in neutropenia and infection. 751 65

The ability of the vascular endothelium to elaborate cytokines in response to gram-positive sepsis has received limited attention. This study examined cytokine expression by human umbilical vein endothelial cells (EC) following infection with a gram-positive bacterial pathogen, Staphylococcus aureus. S. aureus infection of EC resulted in the production of interleukin-6 (IL-6) and IL-1 beta. For IL-6, message was detected at 3 h after infection, protein was present at 24 h, and both message and protein persisted for 72 h. IL-1 beta message was detected at 12 h, IL-1 beta protein was detected at 24 h, and both persisted for 72 h. Message for colony-stimulating factor 1 remained unaltered. UV-killed S. aureus also elicited IL-1 beta and IL-6 message and protein expression at 24 and 48 h. Twenty-one clinical isolates of S. aureus were tested, and all induced IL-6 release by 48 h. However, the laboratory strain 8325-4 did not induce cytokine expression at any time point and was internalized by EC 1,000-fold less than other strains were. Internalization of latex beads by EC did not induce IL-6 gene expression. Furthermore, cytochalasin D treatment of the EC prevented IL-1 and IL-6 induction by S. aureus but not by tumor necrosis factor alpha or lipopolysaccharide. These results indicate that S. aureus is a potent inducer of IL-1 and IL-6 in EC and that internalization of S. aureus by EC is necessary for their cytokine expression. Thus, our data suggest that the vascular endothelium may play an important role in the pathogenesis of septicemia caused by gram-positive organisms.
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PMID:Internalization of Staphylococcus aureus by endothelial cells induces cytokine gene expression. 772 92

The small subset of circulating monocytes that express the maturation-associated CD16 antigen has recently been reported to be elevated in patients with bacterial sepsis. We now show that this novel CD16+ monocyte population is also spontaneously expanded in patients with cancer. We studied 14 patients with metastatic gastrointestinal carcinoma enrolled ina clinical trial of recombinant human macrophage colony-stimulating factor (rhMCSF) plus monoclonal antibody D612. We found that before any cytokine treatment, 12 of 14 patients constitutively displayed significant elevations in both the percentage and the absolute number of CD16+ monocytes, as compared with both normal subjects and ill patients with elevated monocyte counts but without malignancy. CD16+ monocytes accounted for 46% +/- 22% of total monocytes in the patients with cancer versus 5% +/- 3% for controls (P < .01). The increase was not attributable to infection or intercurrent illness and appeared to be associated with the underlying malignancy itself. A similar spontaneous elevation of CD16+ monocytes was observed in 35 of 44 additional patients diagnosed with a variety of other solid tumors. When patients with gastrointestinal carcinoma were treated with rhMCSF, there was a marked further increase in the percentage of CD16+ monocytes (to 83% +/- 11%), as well as in the absolute number of CD16+ cells and the level of CD16 antigen expression. In every case, the patients with cancer showed a greater CD16+ monocyte response than the maximal response obtained in normal volunteer subjects treated witha similar regimen of rhMCSF (n = 5, P < .001), suggesting that the presence of malignancy primed patients for enhanced responsiveness to rhMCSF. We hypothesize that spontaneous expansion of the CD16+ monocyte population may represent a novel biologic marker for a widespread and previously unsuspected host immune response to malignancy.
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PMID:CD16+ monocytes in patients with cancer: spontaneous elevation and pharmacologic induction by recombinant human macrophage colony-stimulating factor. 774 51

Immunity to Listeria monocytogenes, an important pathogen in human neonatal sepsis, is mediated by mononuclear phagocytes, which are regulated by the hematopoietic growth factor colony-stimulating factor 1. Neonates with listeriosis had higher circulating colony-stimulating factor 1 levels and subsequent monocyte counts than those of both noninfected newborns and newborns infected with nonlisterial organisms.
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PMID:Colony-stimulating factor 1 in the human response to neonatal listeriosis. 789 Apr 28

A 75-year-old female was admitted to our hospital because of fever and hypotension. The peripheral blood showed 400 leukocytes/microliters with 13,000/microliters platelets. Bone marrow puncture revealed that NCC stood at 14,000 with 50.0% blasts. The surface characters of the blasts were CD13+, CD33+, and HLA-DR+, and blood culture tests were positive. Coagulation tests revealed DIC. Based on the foregoing results, hypoplastic leukemia was diagnosed accompanied by sepsis and DIC, and was placed on the concomitant administration of a combination of low dose Ara-C and M-CSF. After 14 days of Ara-C administration and 26 days of M-CSF, her clinical symptoms improved, with the peripheral blood showing a WBC of 2,800/microliters and platelet count of 111,000/microliters. The percentage of myeloblasts decreased to 7.0%. After the administration of Ara-C was suspended for 2 weeks, another course of low dose Ara-C plus M-CSF administration was carried out and the patient achieved full remission. M-CSF stimulates not only the production of monocytes but increases the number of neutrophils and platelets through monocytes. It is also expected that tumoricidal activity may be realized by the activation of monocytes. In this patients, the concomitant administration of M-CSF and low dose Ara-C was remarkably effective in treating hypoplastic leukemia with severe complication. This result suggests that M-CSF will be useful for the treatment of leukemia.
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PMID:[Hypoplastic leukemia which achieved remission with administration of M-CSF along with low dose ara-C]. 831 38

The CD16 receptor (Fc gamma R-III) is found on many tissue macrophages (M phi s), but its expression on circulating monocytes is restricted to a small, phenotypically distinct subset. The number of these CD16+ monocytes may be markedly increased in response to sepsis, human immunodeficiency virus infection, or metastatic malignancy. We have recently shown that the CD16+ monocyte population is selectively expanded by administration of recombinant human macrophage colony-stimulating factor (rhM-CSF). In the current study, we used the highly rhM-CSF-responsive cynomolgus primate model to further characterize this novel monocyte population. Animals treated with rhM-CSF underwent a progressive and essentially complete conversion to the CD16+ monocyte phenotype, with up to a 50-fold increase in the number of CD16+ cells. This increase was paralleled by the emergence of a population of circulating cells that morphologically resembled large granular lymphocytes (LGLs). However, quantitatively, this population corresponded closely to the number of CD16+ monocytes, and fluorescence-activated cell sorting (FACS) confirmed that they were the same. In addition to their LGL-like morphology, many rhM-CSF-induced CD16+ monocytes showed a pattern of size, granularity, and quantitative cell surface marker expression that closely resembled the pretreatment LGL/natural killer (NK) cell population but that did not resemble the pretreatment monocyte population. However, rhM-CSF-induced CD16+ monocytes could be distinguished from LGL/ NK cells by fact that they all expressed cell surface receptors for rhM-CSF, and many of them showed reduced but detectable phagocytic and respiratory burst activity. Studies of human subjects treated with rhM-CSF also showed an analogous population of "LGL-appearing" CD16+ mononuclear cells. Thus, our studies reveal a previously unsuspected ability of cells in the monocyte lineage to adopt a phenotype similar to that of LGL/NK cells. The extent of this phenotypic convergence suggests that the two lineages retain access to elements of a similar developmental pathway.
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PMID:Recombinant human macrophage colony-stimulating factor in nonhuman primates: selective expansion of a CD16+ monocyte subset with phenotypic similarity to primate natural killer cells. 869 39

Therapy with colony-stimulating factors has been extended beyond their use in accelerating myeloid cell recovery to take advantage of their immune function-enhancing properties. Studies in animal models and with human subjects suggest a potential role as adjunctive therapy in infections of non-neutropenic hosts, including those with sepsis. Granulocyte colony-stimulating factor may play a pivotal role in the induction of lipopolysaccharide desensitization by nontoxic lipid A analogues proposed for the prevention of sepsis; granulocyte macrophage colony-stimulating factor may be useful in reversing the immune paralysis described in later stages of sepsis. Significant issues of exogenous colony-stimulating factor therapy must be addressed, however: the optimal timing, dose, and clinical context (e.g., type of immunosuppression, duration of infection-inciting stimulus) as well as tissue-specificity of the activities and net effect of potentially conflicting responses (e.g., immune restorative and procoagulant effects of granulocyte macrophage colony-stimulating factor). Resolution of these issues will require carefully designed clinical studies with meticulous monitoring of immunologic parameters.
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PMID:Role of hematopoietic growth factors in non-neutropenic infections and sepsis. 1022 39

We investigate the regulation of plasminogen activator inhibitor-2 (PAI-2) in murine macrophages. PAI-2 mRNA was inducible by bacterial lipopolysaccharide (LPS) in primary cells and macrophage-like cell lines. Evidence is presented for a role for autocrine factors, including cyclooxygenase products but not the cytokines tumor necrosis factor alpha or interferon-beta (IFN-beta). PAI-2 mRNA levels generally varied inversely from those of its target, urokinase-type plasminogen activator (uPA), and the macrophage growth factor CSF-1, which induces uPA, inhibited PAI-2 expression in cells treated subsequently with LPS. Expression of PAI-2 was distinct from that of other LPS-inducible genes in terms of induction time course, LPS dose response, and sensitivity to co-stimulation with IFN-gamma. Induction of PAI-2 mRNA in subclones of the cell line RAW 264 was not uniform, reflecting heterogeneous expression in the parent line. The expression pattern of PAI-2 is discussed in terms of a possible role in LPS-induced pathology such as septicemia.
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PMID:Regulation of the plasminogen activator inhibitor-2 (PAI-2) gene in murine macrophages. Demonstration of a novel pattern of responsiveness to bacterial endotoxin. 1041 Oct 6

Neutropenia in neonates is often associated with sepsis, prematurity and maternal hypertension with increased risk of mortality. We describe two neonates with neutropenia treated with granulocyte macrophage colony stimulating factor. The total and absolute neutrophil counts showed a marked response and led to a favourable outcome. Human granulocyte macrophage colony stimulating factor may be used as an adjuvant therapy for neonatal neutropenia of different aetiologies.
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PMID:Granulocyte macrophage-colony stimulating factor (GM-CSF) in neonatal neutropenia. 1083 25


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