Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The production of TNF alpha by peripheral blood mononuclear cells (PBMC) was determined in 18 hemodialysis (HD) patients. Blood was taken from each patient before and after an HD treatment. Both pre- and post-HD PBMC produced significantly more TNF alpha than controls (TNF alpha units/ml; mean +/- SEM; controls 3.1 +/- 0.7; pre-HD 9.7 +/- 3.9; post-HD 19.8 +/- 7.7, p < 0.05). In addition, post-HD PBMC produced significantly more TNF alpha than pre-HD PBMC suggesting that the HD procedure itself may activate cytokine production. This was true when PBMC were cultured in serum free medium as well as on culture with non-HD sera (human AB) and autologous sera. A positive correlation was also found between the production of TNF alpha and age in HD patients (r = 0.58; p < 0.01). Finally, normal PBMC cultured in post-HD sera produced significantly less TNF alpha than when cultured in the same sera pre-HD (p < 0.02). These findings suggest that PBMC of HD patients are chronically stimulated to produce TNF alpha which may contribute to some of the short-term and long-term complications of HD.
 ...
PMID:Production of tumor necrosis factor alpha and hemodialysis. 824 92

Altered macrophage function after thermal injury is associated with increased production of PGE2 and TNF. However, it is not clear why synthesis of both cellular products remains elevated, as PGE2 is a potent inhibitor of TNF secretion. We studied the relationship between PGE2 and TNF synthesis in a murine model of thermal injury, and examined the effect of prostaglandin blockade on splenic macrophage secretion of these mediators of inflammation. LPS-stimulated production of PGE2 was significantly elevated in burn groups compared with sham-burned controls (pg/ml mean(SEM); sham 151(32): burn 597(147), p < 0.01). TNF production was similarly increased after thermal injury (pg/ml mean(SEM); sham 62(20): burn 928(316), p < 0.01). In vitro culture of macrophages with indomethacin augmented LPS stimulated TNF production in sham-burned controls but did not affect synthesis in burn groups, suggesting a loss of PGE2-dependent regulation of TNF synthesis after thermal injury. Direct measurement of TNF secretion as a function of exogenous PGE2 confirmed this dissociation between PGE2 and TNF synthesis, as burned animals displayed a 5-fold reduction in sensitivity to PGE2-induced inhibition of TNF, when compared with sham-burned controls (ID50 PGE2 molar; sham 1.26 x 10(-8): burn 6.43 x 10(-8), p < 0.05). In vivo pretreatment of burn groups with indomethacin for 5 days before assay partially restored sensitivity to the prostaglandin, and significantly down-regulated synthesis of both TNF and PGE2. These data show that thermal injury is associated with a loss of PGE2-dependent down-regulation of TNF synthesis, which accounts at least in part for increased TNF in these animals. In vivo cyclooxygenase blockade partially restored sensitivity to the prostaglandin and consequently down-regulated synthesis of TNF. These data further support existing evidence that suggests a potential therapeutic role for cyclooxygenase blockade after major thermal injury and trauma.
 ...
PMID:Mechanism of increased tumor necrosis factor production after thermal injury. Altered sensitivity to PGE2 and immunomodulation with indomethacin. 834 98

To determine whether prostaglandins (PGs) mediate the ACTH response to tumor necrosis factor-alpha (TNF alpha), indomethacin (Indo; 0.1-1.0 mg/kg, iv) was administered before TNF alpha (1 microgram, iv) in freely moving, alert rats. While Indo alone did not affect plasma ACTH levels, it dose-dependently blocked the ACTH response to TNF alpha. The highest dose of Indo abolished the ACTH response to TNF alpha [peak plasma ACTH values (mean +/- SEM): buffer/buffer, 137 +/- 34 pg/ml; Indo/buffer, 115 +/- 31; buffer/TNF alpha, 469 +/- 77; Indo/TNF alpha, 120 +/- 27] without modifying the ACTH response to CRF 1 microgram/kg, iv, demonstrating that pituitary responsiveness was unaffected. Since it has been reported that Indo elevates plasma corticosterone (B) levels, the effect of Indo could reflect rapid negative feedback by B, rather than the involvement of PGs. However, inhibition of ACTH secretion was shown to be dependent on the dose of Indo, whereas plasma B levels were elevated to the same degree, independent of the Indo dose. In addition, Indo failed to block the ACTH response to an unrelated ACTH stimulus, insulin-induced hypoglycemia (area under response curve: insulin alone, 31,131 +/- 2,794 pg/min.ml; Indo/insulin, 32,919 +/- 3,582 pg/min.ml). Finally, in adrenalectomized B-replaced rats, TNF alpha elevated ACTH to levels similar to those seen in sham animals, and Indo inhibited these ACTH responses to the same extent in both groups. Thus, Indo inhibited the ACTH response to TNF alpha by a mechanism independent of B feedback. These results indicate that acute systemic administration of TNF alpha stimulates ACTH secretion through a PG-dependent mechanism.
 ...
PMID:Prostaglandins mediate the adrenocorticotropin response to tumor necrosis factor in rats. 838 Mar 77

Addition of recombinant interleukin-1 beta (IL-1 beta) to human long-term bone marrow culture (LTBMC) was found to have a profound effect on adipocyte formation. Control cultures developed 133 +/- 58 adipocytes/flask compared with 3 +/- 2 adipocytes/flask in IL-1 beta-treated flasks (mean +/- SEM, n = 6 for both groups). In terms of cell number, morphology and colony forming cell, IL-1 beta did not have significant effects on LTBMC, although IL-1 beta slightly enhanced colony-stimulating activity of LTBMC-conditioned medium. To further analyze the effect of IL-1 beta on adipocytes, stromal cells were passaged to reduce hemopoietic cell content, and marrow fibroblasts were converted to adipocytes following addition of hydrocortisone. In both types of assay, IL-1 beta again reduced adipocyte formation: control 1095 +/- 76 adipocytes/flask, IL-1 beta-treated 7 +/- 2 adipocytes/flask (n = 3 for both groups). When preformed adipocytes were treated with IL-1 beta for 1 week, the number of lipid-laden cells decreased to 41 +/- 13% of its value before treatment compared to 87 +/- 9% for untreated controls. The addition of neutralizing concentrations of anti-TNF did not inhibit these effects of IL-1 beta. These results suggest that 1) adipocyte formation is not essential for healthy LTBMC growth, or at least IL-1 beta is an effective substitute for adipocytes; 2) IL-1 beta by itself does not significantly enhance hemopoiesis in LTBMC, and this has implications for clinical trials with this cytokine; 3) IL-1 beta produces major changes in stromal cell development, and 4) overgrowth of fat in marrow may reflect defective cytokine regulation in vivo.
 ...
PMID:IL-1 beta inhibits adipocyte formation in human long-term bone marrow culture. 841 58

Recent studies have demonstrated increased levels of IL-6 in the peritoneal cavity during CAPD peritonitis. The current investigation was initiated (i) to examine the human peritoneal mesothelial cell (HPMC) as a possible source of this secreted IL-6 and (ii) to characterize the released product and examine its regulation by other cytokines. Unstimulated HPMC under growth arrested conditions released IL-6 in a time dependent manner. After 24-hour HPMC IL-6 release (mean +/- SEM, N = 13) (expressed as pg/micrograms cell protein) was 1.67 +/- 0.33. Stimulation of HPMC with IL-1 beta or TNF alpha resulted in a time (increasing up to 48 hr) and dose dependent IL-6 generation. After 24 hours the levels induced by IL-1 beta and TNF alpha (both at 1000 pg/ml) were (mean +/- SEM, N = 13) 19.08 +/- 2.98 and 6.62 +/- 1.72, respectively. Stimulation with combinations of IL-1 beta and TNF alpha resulted in additive increases in IL-6 release. This release could be inhibited by co-incubation with anti-IL-1 beta and/or anti-TNF alpha antibodies. The level of released HPMC IL-6 measured by immunometric assay (ELISA) correlated directly with that detected in the 7TD1 IL-6 bioassay (r = 0.63; P < 0.001). Western blot analysis of concentrated HPMC supernatants using specific anti-IL-6 antibody demonstrated immunoreactive bands at 23 and 28 Kd following IL-1 beta or TNF alpha treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Human peritoneal mesothelial cells synthesize interleukin-6: induction by IL-1 beta and TNF alpha. 843 63

We examined the interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) releasability of alveolar macrophages and the natural killer (NK) cell activity in the bronchoalveolar lavage (BAL) cells of 11 patients with Farmer's lung at different stages of the disease. Although there were some variations in the levels of monokine release, macrophages of patients with acute disease secreted significantly higher spontaneous levels of TNF alpha than did a nonfarming control group (p = 0.0002). Conversely, TNF alpha release stimulated by bacterial lipopolysaccharide (LPS) was similar in patients with acute disease when compared with that in normal control subjects. IL-1 was also spontaneously secreted in significantly greater amounts by patients with acute Farmer's lung than by subjects in a control group (p = 0.0001). However, LPS-induced IL-1 release was significantly diminished in BAL macrophages from patients with acute manifestations of the disease when compared with that in control subjects (p = 0.001). Treating hypersensitivity pneumonitis with corticosteroids or by contact avoidance resulted in very significant decrease in spontaneous and LPS-stimulated IL-1 production by BAL macrophages (p = 0.0001 and p = 0.03, respectively), as well as in a decrease in spontaneous TNF alpha release that was also significant (p = 0.01). In addition, BAL cells of patients in the acute phase had a significant NK cell activity (mean +/- SEM of 18.33 +/- 2.65%). Treatment of these patients resulted in an increase in NK cell activity (mean of 40.17 +/- 7.86%), which was significantly different from values of patients with acute disease (p = 0.037).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:A study of monokine release and natural killer activity in the bronchoalveolar lavage of subjects with farmer's lung. 846 30

Neisseria meningitidis infection may present as meningitis or as severe, fulminant sepsis. In order to classify individual patients early according to the expected course of the disease, we developed a score named Neisseria sepsis index [NESI]. The NESI was defined using the parameters heart rate, mean arterial blood pressure, base excess and presence of acute subcutaneous bleeding and/or skin necroses (minimal value [= no evidence for sepsis] NESI 0; maximum value [= most severe sepsis] NESI 8). Seventeen patients with documented, systemic N. meningitidis infection were prospectively assessed for the terminal complement complex (TCC), serum tumour necrosis factor alpha (TNF alpha) levels (as laboratory parameters for severity of sepsis) and NESI score. The evaluation was immediately performed when the patients were admitted to the hospital. The 17 patients showed the following distribution of data: NESI 0 (n = 4), NESI 1 (n = 6), NESI 2 (n = 0), NESI 3 (n = 1), NESI 4 (n = 2), NESI 5 (n = 2), NESI 6 (n = 0), NESI 7 (n = 1), NESI 8 (n = 1). Mortality was 4/17 patients, all had NESI > or = 5. TCC values ranged from 647-6461 ng/ml (normal range: 130-360 ng/ml); and was not correlated to NESI. TNF alpha values ranged from 10-910 pg/ml and were correlated to NESI (r2 = 0.71, n = 17, P < 0.001). In patients with fatal outcome, TNF alpha was 600 +/- 160 pg/ml (mean +/- SEM) and in surviving patients 130 +/- 50 pg/ml (mean +/- SEM). TNF alpha was increased in 15/17 patients when compared to normal controls (< 27 pg/ml). CONCLUSION. The NESI is based on few clinical, objective data, that are available in every hospital. NESI appears to offer an instrument: (1) for making decisions in regard to appropriate monitoring and treatment of vital organ function; and (2) for assessing the quality of care for this life-threatening infection.
 ...
PMID:Definition of a new score for severity of generalized Neisseria meningitidis infection. 858 2

A monoclonal antibody (MAB) against equine tumor necrosis factor-alpha (Eq TNF) was used to investigate the role of TNF in cytokine, eicosanoid, and metabolic responses of Miniature Horses given endotoxin. Plasma concentrations of interleukin 6 (IL-6), lactate, thromboxane A2 metabolite, and prostacyclin metabolite (6-keto-PGF1 alpha) were measured in 10 Miniature Horses given 0.25 microgram of lipopolysaccharide (LPS; Escherichia coli O55:B5)/kg of body weight. Five horses were given Eq TNF MAB and 5 were given isotype-matched MAB as control. All horses were given 1.86 mg of antibody/kg by IV infusion, 5 minutes before LPS was given IV. Blood samples were taken 20 minutes before and at multiple intervals for 24 hours after LPS was given. Interleukin 6 bioactivity in plasma was measured, using IL-6-dependent cell line (B9). Eicosanoid activities were assessed by enzyme immunoassay, and plasma lactate concentration was determined enzymatically. Data were analyzed by ANOVA and Tukey's honest significant difference test for significant (P < 0.05) effect of treatment. Horses given Eq TNF MAB had significantly (P < 0.050) lower peak mean +/- SEM IL-6 (59 +/- 29 U/ml), lactate (16 +/- 2.00 mg/dl), and 6-keto-PGF1 alpha (254 +/- 79 pg/ml) values then did horses given control MAB (880 +/- 375 U/ml for IL-6; 26 +/- 0.04 mg/dl for lactate; and 985 +/- 290 pg/ml for 6-keto-PGF1 alpha). There was no effect of anti-TNF treatment on LPS-induced thromboxane A2 metabolite production. Tumor necrosis factor mediated IL-6, lactate, and prostacyclin responses, without affecting thromboxane production in horses given LPS.
 ...
PMID:Effects of tumor necrosis factor blockade on interleukin 6, lactate, thromboxane, and prostacyclin responses in miniature horses given endotoxin. 858 54

Soluble receptors for TNF (sTNF-R) are present at elevated concentrations in the synovial fluid of patients with rheumatoid arthritis. They are presumably released by cells of the synovial membrane, including the monocyte-derived synovial macrophages. Cytokines from the synovium, including IL-1 and TNF-alpha, may stimulate release. We therefore examined the release of sTNF-R from monocytes exposed to IL-1 and TNF-alpha. Elutriator-purified human blood monocytes spontaneously released both the p75 and the p55 sTNF-R (1011 +/- 199 and 177 +/- 20 pg/10(6) cells, respectively, mean +/- SEM) during 48 h of in vitro culture. TNF-alpha and IL-1 alpha induced time- and concentration-dependent increases in the release of sTNF-R75 from monocytes, but neither had a measurable effect on the release of sTNF-R55. The release of sTNF-R75 was inhibited by cycloheximide. Neither lymphocytes nor polymorphonuclear leukocytes (PMN) released measurable sTNF-R spontaneously or in response to stimulation with IL-1 alpha, but TNF-alpha stimulated the release of small amounts of sTNF-R75 by PMN. The timing, cycloheximide sensitivity, and selectivity of stimulated release of TNF-R75 by monocytes are consistent with previous observations on other cell types of late (8-20 h) increased synthesis and turnover of cell surface TNF-R75, but not TNF-R55, after stimulation with TNF-alpha or IL-1. These observations help to explain why elevated levels of sTNF-R in synovial fluid coexist with enhanced expression of cell surface TNF-R on synovial macrophages in rheumatoid arthritis.
 ...
PMID:Tumor necrosis factor alpha and interleukin-1 alpha stimulate late shedding of p75 TNF receptors but not p55 TNF receptors from human monocytes. 859 Mar 6

The use of IL-1 in humans is associated with dose-limiting toxicity which resembles that of TNF-alpha or IL-2. Activation of neutrophils is thought to contribute to the toxicity caused by these two cytokines. We studied the effect of IL-1 in vivo on changes in neutrophil numbers and neutrophil degranulation as well as on the formation of neutrophil agonists, such as complement activation products, and on levels of TNF, IL-6, IL-8, and nitrite/nitrate (as a measure of nitric oxide production). Six patients with metastatic melanoma were treated with 3 ng/kg recombinant human IL-1 beta daily. One hour after the start of the 30-min IL-1 infusion, which caused mild cardiovascular toxicity, plasma levels of IL-6 reached a peak of 25 +/- 9 ng/L (mean +/- SEM), IL-8 reached a peak of 311 +/- 100 ng/L at 2 h, and nitrite/nitrate peaked after 10 h to 89 +/- 27 mumol/L. IL-1 did not induce significant changes in plasma levels of TNF or of the complement activation products C3a and C4b/c. Although IL-1 induced neutrophilia, levels of elastase and lactoferrin did not change. The failure of IL-1 to degranulate neutrophils was confirmed in an ex vivo model with whole blood culture in which doses of up to 100 microgram/L IL-1 beta or IL-1 alpha failed to induce significant elastase or lactoferrin release, whereas TNF, tested as a positive control, was able to do so. These results demonstrate that, unlike TNF, IL-1 does not cause neutrophil degranulation in man, despite its ability to cause neutrophilia and the rapid release of IL-6, IL-8, and nitrite/nitrate.
 ...
PMID:IL-1 beta does not cause neutrophil degranulation but does lead to IL-6, IL-8, and nitrite/nitrate release when used in patients with cancer. 859 89


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