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)

IL-4 has been found to affect the phenotype and a variety of functions of human monocytes and macrophages and has been discussed as a monocyte activating protein along with other cytokines, such as IL-1 and IL-6. In this study we compared the effects of the cytokines IL-1, IL-6, IL-4, and a combination of IL-1 and IL-6 on the expression of the CD14 antigen, the FcIIIg receptor molecule CD16 and the MHC-class II molecules HLA-DR and HLA-DP. These molecules represent characteristic monocyte surface markers. Furthermore, the CD14 molecule has been described as a surface antigen of high in vivo relevance representing an indirect receptor for LPS. We further analyzed the effect of IL-4 on monocytes and macrophages with respect to their accessory function to initiate T-lymphocyte proliferation. Human peripheral blood monocytes strongly express the antigen CD14 and maintain it as a stable surface molecule during their differentiation to macrophages. Flow cytometry analysis of cultured monocytes demonstrated that cells incubated in the presence of IL-4, but not IL-1 and/or IL-6 revealed a reduced expression of the CD14 antigen in a dose- and time-dependent manner. After 3 days IL-4 treated cells were virtually CD14-negative. At the same time the expression of the CD16 antigen (FcRIIIg) was also strongly reduced, whereas the treatment with IL-4 led to an increased expression of MHC class II antigens such as HLA-DR and HLA-DP. The spontaneous low expression of HLA-DQ antigen on monocytes was not affected by any of the cytokines. Functionally, IL-4 treated CD14-negative monocytes exhibited a more than 2-fold higher activity to stimulate an accessory cell-dependent T cell proliferation. This was found in a mitogenic assay and in MLC when compared to monocytes cultured in the absence of IL-4. These observations provide further evidence that IL-4 is a major modulator of monocyte surface antigen expression. Moreover, IL-4 has an enhancer-effect on monocytes as accessory cells and therefore may be of considerable importance as a regulatory factor during monocyte development to accessory cells. Inasmuch as the CD14 molecule functions as a receptor for LPS-binding protein, our results suggest that IL-4 might also play an important regulatory role in processes initiated by bacterial lipopolysaccharides during inflammation and sepsis.
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PMID:IL-4 decreases the expression of the monocyte differentiation marker CD14, paralleled by an increasing accessory potency. 171 65

The destruction of proliferating lymphoid cells within germinal centers with subsequent replacement by histiocytoid cells has been described in infants and children dying of viral and bacterial infections. The etiology and significance of "epithelioid germinal centers" (EGCs) are unknown. The cells implicated in forming EGCs have included histiocytes and dendritic reticulum cells. We have studied four children at autopsy who died at ages ranging from 10 months to 7 years. Three contracted fatal infections, one with fulminant meningococcemia, one with bacterial sepsis, and one with viral hepatitis. The fourth child contracted viral pneumonitis and died of acetaminophen toxicity. Epithelioid germinal centers were found in numerous lymphoid organs (spleen, lymph nodes, and Peyer's patches) in all four cases. Avidin-biotin complex immunohistochemical analysis performed on formalin-fixed splenic tissue from the first three cases and snap-frozen splenic tissue from the second case revealed an absence of B cells in the follicular centers. The mantle zones surrounding follicles were thin but intact. The histiocytoid cells expanding the germinal centers were positive for S100 and R4/23 (dendritic reticulum cells) and negative for numerous histiocyte markers (alpha 1-antitrypsin, alpha 1-antichymotrypsin, and lysozyme). Increased numbers of killer cells (Leu-7) were present within the affected germinal centers in the three cases in which material was available for immunohistochemical studies. Overwhelming infections in these patients seem to result in anomalous natural killer cell activation resulting in localized nonselective destruction of follicular centers similar to anomalous natural killer cell activity reported to occur in fatal infectious mononucleosis. This may lead to an acquired immunodeficiency that precludes long-term survival in affected patients.
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PMID:Epithelioid germinal centers in overwhelming childhood infections. The aftermath of nonspecific destruction of follicular B cells by natural killer cells. 284 41

Sepsis is a major factor in the high mortality and morbidity after surgery for obstructive jaundice. Several studies have suggested that reticuloendothelial function is depressed, but changes in lymphocyte function are poorly understood. A model of obstructive jaundice has been produced by chronic common bile duct ligation in eight dogs. In vitro lymphocyte studies were performed both at 2 and 3 weeks duration of jaundice and compared with simultaneous healthy control subjects. Icteric animals showed no abnormality of natural killer cell function. Relative numbers of T and B lymphocytes and their subsets were unchanged. T lymphocyte responses to three mitogens were not significantly reduced in jaundiced animals. Serum immunoglobulin levels were unchanged compared to those before surgery apart from a significant rise in immunoglobulin A. No evidence of circulating immunosuppressive factors was found by mitogen testing on normal lymphocytes in the presence of pooled serum from jaundiced animals, normal serum, or normal serum with added bilirubin. Our study does not suggest that impairment of lymphocyte function contributes significantly to the dangers of sepsis in obstructive jaundice.
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PMID:Lymphocyte function in obstructive jaundice. 292 63

Staining with CD14 and CD16 monoclonal antibodies will identify two monocyte subpopulations in human blood: a major population of regular monocytes, which strongly expresses the CD14 antigen (CD14++), and a minor population with weak expression of CD14 and expression of the CD16 antigen (CD14+/CD16+ cells). As shown herein, the latter cells account for 45 +/- 22 cells/microL and 9% +/- 5% of the monocytes in healthy control donors (n = 35). In septicemia patients, the CD14+/CD16+ cells can become a major population, with more than 50% of all monocytes in 3 of 18 patients and with more than 500 cells in 4 of 18 cases. There was no correlation of CD14+/CD16+ cells to any clinical parameter except for CD14+/CD16+ percentage and body temperature (P = .013). The CD14++ regular monocytes showed a substantial decrease in CD14 antigen density in 9 of 11 patients. Three-color immunofluorescence shows that the CD14+/CD16+ monocytes in septicemia patients when compared with the CD14++ monocytes exhibit a higher level of class II antigen and a lower level of CD11b and CD33 antigens, consistent with a more mature nature of the CD14+/CD16+ cells. Levels of interleukin-6 (IL-6) were increased in septicemia patients; 3 of 5 patients with high numbers of CD14+/CD16+ cells (> 200/microL) had high levels of IL-6 (> 250/U/mL). These data suggest that septicemia may lead to substantial changes in blood monocyte composition and this may be related to elevated levels of cytokines such as IL-6.
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PMID:The novel subset of CD14+/CD16+ blood monocytes is expanded in sepsis patients. 769 40

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

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.
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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

We describe a 69-year-old Japanese male with acute leukemia with a CD7+ and CD56+ immunophenotype presenting with multiple lymphadenopathy. He was treated with idarubicin and cytosine arabinoside. Although the leukemia showed partial response, the patient did not achieve complete remission. He died of sepsis due to severe neutropenia after the third course of chemotherapy. His autopsy revealed blast infiltration in the lymph nodes, liver, spleen and vertebral bone marrow. Recently, CD7+ and CD56+ myeloid/natural killer precursor acute leukemia has been associated with a poor prognosis. Our case illustrates that myeloid/natural killer cell precursor acute leukemia shows some response to intensive chemotherapy for acute myeloid leukemia, but such therapy is insufficient to effect a cure. To overcome the resistance of this disease to chemotherapy, further studies should explore other treatment strategies.
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PMID:CD7+ and CD56+ myeloid/natural killer cell precursor acute leukemia treated with idarubicin and cytosine arabinoside. 1214 68

Triggering receptor expressed on myeloid cells (TREM)-1 is a recently identified molecule that is involved in monocytic activation and in the inflammatory response. It belongs to a family related to the natural killer cell receptors and is expressed on neutrophils, mature monocytes and macrophages. The inflammatory response mediated by Toll-like receptor-2 and -4 stimulation is amplified by the engagement of TREM-1. The expression of membrane-bound TREM-1 is greatly increased on monocytes during sepsis. Moreover, infection induces the release of a soluble form of this receptor, which can be measured in biological fluid and may be useful as a diagnostic tool. Modulation of the TREM-1 signalling pathway by the use of small synthetic peptides confers interesting survival advantages during experimental septic shock in mice, even when this teatment is administered late after the onset of sepsis.
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PMID:Clinical review: role of triggering receptor expressed on myeloid cells-1 during sepsis. 1627 37

The triggering receptor expressed on myeloid cells (TREM)-1 is a recently identified molecule that is involved in monocytic activation and the inflammatory response. It belongs to a family related to natural killer cell receptors, and is expressed on neutrophils, mature monocytes and macrophages. The engagement of TREM-1 synergizes with the activation of several toll-like receptors in amplifying the inflammatory response mediated by microbial components. The modulation of the TREM-1 signaling pathway, by the use of small synthetic peptides derived from its extracellular domain, confers interesting survival advantages during experimental murine septic shock, even when administered late after the onset of sepsis.
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PMID:The therapeutic potential of TREM-1 modulation in the treatment of sepsis and beyond. 1672 20

Multiple myeloma is associated with a high risk of infections. We hypothesized that Fc gamma receptor (FCGR) and myeloperoxidase (MPO) promoter gene polymorphisms influence the risk of infections after induction chemotherapy (IC) and autologous stem cell transplantation (ASCT). Retrospectively, we analysed 136 patient courses of IC and 113 procedures of ASCT. Genetic analyses were made with PCR techniques on genomic DNA. The incidence rate ratio of sepsis during ASCT in patients homozygous for the G-129MPO promoter type was 0.30 (95% CI: 0.09-0.96). The G-463AMPO promoter polymorphism was not associated with the risk of infections. The polymorphisms of FCGR2A, FCGR3A and FCGR3B were not convincingly associated with infections. The NA1 variant of FCGR3B was strongly skewed with other risk factors, and the results in IC and ASCT were conflicting. Further studies of the G-129AMPO promoter as a potential risk modifier for infections are relevant.
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PMID:Infectious complications after chemotherapy and stem cell transplantation in multiple myeloma: implications of Fc gamma receptor and myeloperoxidase promoter polymorphisms. 1845 2


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