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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The generation of tumour necrosis factor (TNF) and tissue factor activity in lipopolysaccharide (LPS) stimulated blood were studied in 25 healthy subjects before and after physical exercise of different intensities. Of the subjects a group of 9 were athletes who trained once to twice every day of the week, a second group of 8 exercised 3-7 times a week, and a third group of 8 exercised 4-5 times a month. The production of TNF in freshly drawn LPS stimulated blood in heparin, drawn from top athletes at rest was significantly lower than in the other subjects. The LPS induced concentrations of TNF-alpha of 2.73 (SEM 1.05) ng.ml-1 in the blood of the top athletes compared to 5.08 (SEM 0.7) ng.ml-1 and 7.6 (SEM 1.6) ng.ml-1, respectively, in the other two groups. The group that trained the least had the highest values. Immediately after exercise, the monocytes appeared to be less responsive to LPS stimulation, as a reduction of 47%-48% was observed in the top athletes and in the other group of well-trained individuals. The group that trained the least, which was also subjected to the least stressful exercise, had a 33% reduction in TNF production. Within 6 h the TNF concentration was back to pre-exercise values. Within 6 h the TNF concentration was back to pre-exercise values.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in blood cell response following strenuous physical exercise. 159 56

We have previously reported that the combination of IFN-gamma plus TNF-alpha is able to induce the de novo expression of HLA class II on human beta cells. In the present study, we have investigated the effect of these cytokines, alone or in combination, on the function and viability of human islet cells in vitro. Three hour insulin release was markedly reduced in human islet monolayer cultures after 4 days' exposure to 1000 U/ml of the combination TNF-alpha plus IFN-gamma (36.7 +/- 7.7, % of the control +/- SEM) or to TNF-alpha alone (49.5 +/- 7% of the control) while IFN-gamma had little effect. On direct inspection cell damage was clearly detected only in the cultures treated with TNF-alpha plus IFN-gamma in which staining by indirect immunofluorescence (IFL) for insulin revealed that the number of beta cells was also significantly reduced, thus suggesting a real cytotoxic effect of this cytokine combination. This effect was not beta cell specific since glucagon release and the number of alpha cells were also reduced in the cultures exposed to IFN-gamma plus TNF-alpha. 51Cr release experiments supported the cytoxicity of these cytokines to normal islet cells. There was a time course relationship between class II induction (2 days) and the cytotoxic effect of IFN-gamma plus TNF-alpha (4 days) on the same islet cells. In conclusion, these results indicate that the combination of IFN-gamma and TNF-alpha exerts a cytotoxic effect on human islet cells in vitro.
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PMID:Cytotoxic effect of IFN-gamma plus TNF-alpha on human islet cells. 190 37

Cachectin-tumor necrosis factor (TNF-alpha) has been implicated as a possible signal for the initiation of human parturition in the setting of infection. These studies were conducted to determine whether human decidua can produce TNF-alpha in response to bacterial lipopolysaccharide (LPS). Decidual explants from women undergoing elective cesarean sections were incubated with and without Escherichia coli LPS (25 ng/ml) for 20 h. TNF-alpha concentration in the conditioned media was measured with an enzyme-linked immunoassay and bioassay (L929 bioassay). While conditioned media from unstimulated decidual explants contained either undetectable or low levels of TNF-alpha, conditioned media from LPS stimulated decidua contained TNF-alpha (mean = 2.6 pmol/mg protein per 20 hours, SEM +/- 1.03). There was a strong correlation between the immunoreactive and bioactive TNF-alpha (Spearman rank correlation r = 0.76, P less than 0.001). We conclude that human decidua in vitro can produce TNF-alpha in response to LPS.
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PMID:Human decidua: a source of cachectin-tumor necrosis factor. 193 92

An agar plating technique was developed for enumeration of IL-1-producing monocytes based on the principle that when IL-1-producing monocytes were cocultured with mouse thymocytes and PHA in semisolid agar medium in a plate, mouse thymocytes proliferated around IL-1-producing monocytes resulting in the clusters or colonies of cells. The IL-1-produced clusters or colonies of cells can be counted under a dissecting microscope. Optimal conditions were established for induction and development of IL-1-producing monocytes. The numbers of IL-1-producing monocytes ranged from 819 to 1930 cells/10(5) monocytes, with mean +/- SEM = 1344 +/- 182 cells/10(5) monocytes; the IL-1 activity ranged from 11.7 to 85.9 U/10(5) monocytes/ml, with mean +/- SEM = 42.8 +/- 11.2 U/10(5) monocytes/ml in seven normal subjects. The IL-1 activity per one monocyte ranged from 12.7 to 86.5 mU, with mean +/- SEM = 33.5 +/- 9.8 mU. The mean numbers of IL-1-producing monocytes and the mean IL-1 levels produced by monocytes from the same normal subjects were highly correlated (r = 0.981). The numbers of IL-1-produced colonies resulting from IL-1-producing monocytes could be completely abolished by incorporation of rabbit anti-human IL-1 in the semisolid agarose but not by rabbit anti-human IL-6 or anti-human TNF-alpha.
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PMID:Enumeration of interleukin-1 producing monocytes from human peripheral blood mononuclear leukocytes by agar plating technique. 206 64

By the production of microbicidal agents, such as reactive oxygen species, activated PMN are capable of inducing tissue damage in the host. TNF-alpha was recently shown to be a potent activator of PMN oxidative metabolism. To further evaluate the interaction between activated PMN with physiological target cells, the effect of human PMN on cultured bovine aortic and human umbilical vein endothelial cells (EC) upon stimulation with human TNF-alpha was investigated by ultrastructural techniques: Scanning and transmission electron microscopy (SEM and TEM resp.) and ultrastructural detection of H2O2 production. When isolated PMN were added to EC in the presence of recombinant human TNF-alpha (10(3) U/ml) the EC-monolayer was disrupted within 4 h and EC changed their shape by exhibiting a spindle-like structure. PMN were seen in the intercellular spaces. Release of H2O2 was observed at the surface of the PMN plasma membrane, the luminal part of the small intracytoplasmic vacuoles in the PMN as well as in the contact zone between PMN and EC, but not within the EC. Scavengers of reactive oxygen species, such as superoxide dismutase and catalase or D-mannitol failed to block the effect of TNF-alpha-stimulated PMN on EC. In contrast, addition of NaN3 (0.1 mM), an inhibitor of myeloperoxidase activity, almost completely inhibited the disruption of EC-monolayers. Subsequent addition of NaN3-insensitive horseradish peroxidase reconstituted the effect. The results obtained suggest that TNF-alpha-stimulated PMN effectively cause the disruption of EC monolayers by an adherence-dependent mechanism which is mediated by the release of myeloperoxidase. The results may be of major importance for the pathogenesis of inflammatory vascular reactions.
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PMID:Interaction of granulocytes and endothelial cells upon stimulation with tumor necrosis factor-alpha: an ultrastructural study. 209 2

In the previous study we demonstrated that circulating levels of TNF-alpha are elevated during liver allograft rejection and may precede clinical manifestations. The current study was designed to investigate the efficacy of antibody therapy against tumor necrosis factor-alpha and lymphotoxin (LT) in a rat heterotropic cardiac transplant model utilizing Buffalo donors and Lewis recipients. Control animals received no immunotherapy and experienced rejection on postoperative day 11 +/- 0.4 (mean +/- SEM). Experimental animals received immunotherapy either intraperitoneal or intravenous from days 1 to 10. The i.p. administered anti-TNF-alpha prolonged graft survival to 16 +/- 2.7 days (P less than 0.05 vs. controls); the i.v. administration prolonged survival to 15 +/- 1.4 days (P less than 0.004). Animals treated with i.p. anti-LT survived 17 +/- 1.7 days (P less than 0.002 vs. controls). Combination immunotherapy of anti-TNF-alpha and anti-LT increased function to 21 +/- 2.2 days (P less than 0.001 vs controls). Conversely, administration of purified TNF-alpha or LT to graft recipients accelerated the time to rejection. Mean survival for both treatments was 7 days (P less than 0.001 vs. controls). Histologic examination of the transplanted cardiac tissue showed a typical pattern for acute rejection; there was no evidence of hemorrhagic or coagulative necrosis. In contrast, administration of purified TNF-alpha or LT to recipients of a syngeneic heart did not stimulate rejection. These data suggest that TNF-alpha and LT may play a role in the pathogenesis of acute allograft rejection. In addition, the mechanism appears to be distinct from that seen in TNF-alpha or LT-mediated cytotoxicity of tumor cells.
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PMID:The role of tumor necrosis factor in allograft rejection. II. Evidence that antibody therapy against tumor necrosis factor-alpha and lymphotoxin enhances cardiac allograft survival in rats. 220 Jan 73

Mortality of the septic syndrome is around 40-60% and can rise to 100% if multiple organ failure (MOF) develops. It is generally assumed that the high mortality of sepsis can only be reduced by early diagnosis and prevention of subsequent MOF. The aim of our study was to investigate the validity of routine TNF-alpha determination for the diagnosis of septicemia and, in combination with clinical scoring systems [MOF score and Acute Physiological and Therapeutic Intervention Score (APATIS)], to define a "therapeutic window" during which an anti-TNF-alpha agent could be applied with the greatest chance of success. METHODS. TNF-alpha serum levels were measured and APATIS and MOF scores were calculated daily in 87 ICU patients. TNF-alpha serum levels were determined by means of an immunoradiometric assay (TNF-alpha IRMA, Medgenix, Belgium). Sepsis was diagnosed in 24 patients according to clinical criteria. To quantify the severity of sepsis, we set up the APATIS. The MOF score was used to assess the severity of MOF. Data were analyzed using the SAS software package (SAS Institute, Cary, N.C.) and are expressed as mean +/- SEM. RESULTS. The mean values of all sequential TNF-alpha determinations were significantly higher in the septic patients compared to the nonseptic patients (73.2 +/- 4.3 vs 8.5 +/- 0.4 pg/ml; P less than 0.01). Similarly, the maximum TNF-alpha values were significantly higher in the septic group (156.9 +/- 26.5 vs 20.1 +/- 1.3 pg/ml; P less than 0.01). To differentiate between sepsis and nonsepsis we set the cut-off point at a TNF-alpha serum level of 40 pg/ml and calculated a sensitivity of 70.8%, a specificity of 98%, and a diagnostic accuracy of 91.3%. None of the patients with a maximum TNF-alpha level above 250 pg/ml survived. Mortality was 80% above a maximum TNF-alpha serum concentration of 200 pg/ml, whereas only 40% of patients with a TNF-alpha maximum below 150 pg/ml died. The mean APATIS and MOF scores were significantly higher for septic than for nonseptic patients (APATIS: 20.3 +/- 0.5 vs 8.1 +/- 0.2 and MOF: 9.8 +/- 0.1 vs 4.6 +/- 0.1). To differentiate between survival and nonsurvival, we set the cut-off point at 25 for APATIS and calculated a sensitivity of 79% and a specificity of 93%. At a MOF score of 8, the sensitivity was 89% and the specificity 82%. In our series cumulative mortality at a maximum MOF of less than 8 was 4% and at MOF greater than 10, 68%. We found an interval of 2.9 +/- 0.9 days between the time TNF-alpha serum levels first exceeded 40 pg/ml and the development of severe MOF (MOF greater than 10) in 13 patients. CONCLUSION. Sequential TNF-alpha serum level determinations are useful for the diagnosis and prognosis of septicemia. We found an interval of 3 days between rising TNF-alpha serum levels and the development of severe MOF. This latency may represent the "therapeutic window" during which an anti-TNF-alpha-agent, e.g., a monoclonal anti-TNF-alpha-antibody, could be applied as a therapeutic consequence.
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PMID:[Is TNF-alpha "ripe" for routine diagnosis in sepsis?]. 227 76

Plasma levels of tumor necrosis factor-alpha were measured in 50 adult patients following orthotopic liver transplantation. The mean (+/- SEM) plasma concentration of TNF-alpha was significantly higher in patients experiencing a rejection episode (941 +/- 83 pg/ml) than in those with a stable clinical course (240 +/- 6 pg/ml; P = 0.0001). Peak levels of TNF-alpha were usually found at the time of clinically diagnosed rejection, although elevated levels were observed 1-2 days earlier. First-week peak TNF-alpha levels were significantly higher in patients who suffered graft loss (2146 +/- 788 pg/ml) than in those who were discharged from the hospital without clinical evidence of rejection (581 +/- 93 pg/ml; P = 0.004). TNF-alpha levels were not correlated with white blood cell count (r2 = 0.004), cyclosporine levels (0.01), serum creatinine (0.002), serum bilirubin (0.05), serum SGOT (0.03), or SGPT (0.05). TNF-alpha levels were not elevated in four cases of viral hepatitis occurring after transplantation. We conclude that circulating levels of TNF-alpha are elevated during liver allograft rejection and may precede clinical manifestations. First-week TNF-alpha levels are also useful predictors of long-term graft outcome. Further investigation is required to determine whether this monokine is important in the actual pathogenesis of allograft rejection.
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PMID:The role of tumor necrosis factor in allograft rejection. I. Evidence that elevated levels of tumor necrosis factor-alpha predict rejection following orthotopic liver transplantation. 238 88

Protectin (CD59) is a low molecular weight glycophosphoinositol-anchored inhibitor of the membrane attack complex of complement (MAC) that is present, for example, on the membranes of endothelial cells and on epithelial cells of glomeruli and distal tubuli. To examine for the possibility that CD59 becomes detached from cell surfaces following cell injury, this study evaluated renal excretion of CD59 in patients with idiopathic membranous glomerulonephritis (MGN; N = 21), diabetic nephropathy (DNP; N = 15) and in healthy control subjects (N = 13). CD59 in human urine was quantitated by a competitive solid-phase radioimmunoassay having approximately 13 kDa soluble urinary CD59 as a standard. Immunofluorescence microscopy demonstrated a decreased expression of CD59 in the glomeruli of MGN patients. Using a Triton X-114 phase separation method 91 to 97% of urinary CD59 was found to be in a soluble form without anchor-associated phospholipid. The mean (+/- SEM) level of urinary CD59 was 5.6 +/- 0.2 micrograms/ml in MGN patients, 3.7 +/- 0.4 micrograms/ml in healthy controls (P < 0.001) and 2.6 +/- 0.1 in DNP patients (P < 0.001). When related to urinary creatinine (UCr) the corresponding values were 11.9 +/- 5.6, 4.8 +/- 0.3 (P = 0.021) and 4.4 +/- 0.2 (P < 0.002), respectively. The amount of CD59 in urine correlated with the urinary excretion of soluble terminal complement complexes, SC5b-9 (r = 0.594, P < 0.006) in MGN patients. The excretion of CD59 also correlated with the excretion of the inflammatory mediator IL-1 beta (r = 0.671, P = 0.001) but not with TNF-alpha (r = 0.314, P = 0.178). No correlation of CD59 excretion was observed with duration of the disease level of proteinuria, serum albumin concentration or serum creatinine level. Based on these findings we speculate that the increased excretion of CD59 into urine in MGN patients is due to complement activation and inflammation induced shedding of CD59 from glomerular cells.
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PMID:Urinary excretion of protectin (CD59), complement SC5b-9 and cytokines in membranous glomerulonephritis. 754 24

Transforming growth factor (TGF)-beta has several downregulatory functions on the immune system: inhibition of interleukin-2 receptor induction, decrease of interferon-gamma-induced class II antigen expression, inhibition of macrophage activation, as well as cytotoxic and lymphokine-activated killer cell generation. TGF-beta has also been recognized as an important immunoregulator in murine leishmaniasis, for which it increases susceptibility to disease. In the present study we evaluate the involvement of TGF-beta in human leishmaniasis in vitro and in patients with cutaneous leishmaniasis. Human macrophages produce active TGF-beta after infection by Leishmania amazonensis (480 +/- 44.7 pg/ml; mean +/- SEM), L. donovani chagasi (295 +/- 7.6 pg/ml), or L. braziliensis (196 +/- 15.7 pg/ml). When TGF-beta was added to cultures of human macrophages infected with L. braziliensis it led to an increase of approximately 50% in parasite numbers as compared with untreated cultures. Exogenous TGF-beta added to macrophage cultures was able to reverse the effect of interferon-gamma in controlling Leishmania growth. Even at 100 IU/ml interferon-gamma the presence of TGF-beta increases the number of intracellular parasites. On the other hand, TNF-alpha at high concentration (100 IU/ml) totally blunts the suppressive effect of TGF-beta. Immunostaining for TGF-beta was observed in the dermis, produced by fibroblasts and occasionally by inflammatory cells in the biopsies from human leishmaniasis lesions, being present in most of the biopsies taken from patients with early cutaneous leishmaniasis (less than 2 months of ulcer development) and in cases of active mucosal leishmaniasis. Taken together these observations suggest an important role for TGF-beta in human leishmaniasis, with its production by infected macrophages being probably related to parasite establishment in the early stages of the disease.
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PMID:Transforming growth factor-beta in human cutaneous leishmaniasis. 757 70


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