Serum tumor necrosis factors TNF

Ding-feng Z, Hong R, Xiao-ping J, Ya-su Z (1993) Serum tumor necrosis factor (TNF) in the pathogenesis of clinical hepatic failure of HCV and/or HBV infection. Chin Med J 106 335-338... 

Radiation-induced immune reaction or cytokines might affect tumors outside of the radiation field and under rare circumstances cause a significant outcome. Ohba et al. described a man who underwent radiation therapy for bone metastasis from hepatocellular carcinoma (Ohba etal. 1998). Surprisingly, regression of the non-irradiated primary tumor was observed. A rise in the serum tumor necrosis factor (TNF)-a after radiotherapy coincided with the response of the primary tumor and an immune response induced by TNF-a was suggested by the authors. Several cases of abscopal effects have been reported for leukemias and lymphomas after radiation therapy. One possible mechanism that is relevant mainly to leukemias and lymphomas is that the distant effect observed is due to the circulation of diseased lymphocytes through the field of local irradiation. 

A Reuter, et al. Radioimmunoassay of tumor necrosis factor TNF-alpha and its clinical application by direct determination in serum. J Leukoc Biol 42 604, 1987. 

Fig. 6. The role of endogenous tumor necrosis factor TNF) in D-galactosamine (GalN)-induced liver damage. All mice were injected with 2.1 g/kg GalN. Serum transaminases ALT) and hepatic DNA fragmentation were determined after 24 h. Animals pretreated with neutralizing anti-TNF antibodies or mice lacking TNF receptor-1 tnf-rl°) were protected...

Fig.4.50 Serum tumor necrosis factor alpha (TNF-a) levels by treatment group and controls (From CavaUini et aL [18])...

Extracts of leaves of Combretum quadrangulare showed promising hepatoprotective effect on D-GalN or tumor necrosis factor-a (TNF-a)-induced cell death in primary cultured mouse hepatocytes. The hepatoprotective effect of C-glycosylflavones from C. quadrangulare was determined by evaluation of the serum enzyme level in comparison with the o-GalN or TNF-a treated control. At the concentration of 200 pg/ml, orientin and isoscoparin possessed an inhibitory effect on TNF-a-induced cell death of about 20%, while vitexin at 100 pg/ml produces a 95%i inhibitory effect. 

In 1975, Lloyd Old and colleagues discovered that transfer of serum from the blood of donor mice that had been previously injected with endotoxin into recipient mice harboring tumors would induce necrosis of the tumors. They dubbed the transferrable substance responsible tumor necrosis factor , or TNF. Remarkably, TNF was also shown to... 

PAOP pulmonary artery occlusion pressure P-gp P-glycoprotein RAA renin-angiotensin-aldosterone RVF right ventricular failure SDC serum digoxin concentration S VR systemic vascular resistance TNF-a tumor necrosis factor-a TZD thiazolidinedione VAD ventricular assist device... 

Following treatment of patients with rheumatoid arthritis with low and high dose anti tumor necrosis factor-a (TNF) or placebo, serum MMP-1 and MMP-3 levels were assessed by Brennan et al. (BIO). In both antibody-treated groups, a significant decrease in serum MMP-3 levels at all time points was observed, reduced maximally to 41% of pre-infusion values at day 7. MMP-1 levels were also reduced, but less dramatically than with MMP-3. While serum MMP-3 levels correlated with C-reactive protein both prior to and following therapy, Brennan et al. concluded that it remains to be demonstrated that serum MMP-3 and/or MMP-1 levels reflect the cartilage and bone resorptive processes which are evident in this disease. Catrina et al. (C2) also examined the effect of anti-tumor necrosis factor-a therapy (etanercept) on MMPs. Etanercept therapy downregulated serum... 

Sometimes, hyperbilirubinemia without mechanical obstruction of the biliary tree is encoimtered postoperatively patients with this complication often suffer from bacterial infections and endotoxemia, which results in stimulation of Kupffer cells to secrete tumor necrosis factor-a (TNF-a) and interleukin (IL)-6. In a study by Ikeda and coworkers (Ikeda, Mitaka et al. 2003), bile was collected from rats treated with or without these cytokines. The livers, perfused with lanthanum after the injection of the cytokines, were examined ultrastructurally. In rats treated with cytokines, the total serum bile acid concentration increased and lanthanum temporarily accumulated in the bile canaliculi, which suggests that the cytokines may reduce bile canaliculi contractions and thereby decrease bile flow. 

The advantages and disadvantages of each method were systematically analyzed. The protein targets examined included Smad proteins (which play a role in cardiac muscle development) and various regulatory proteins found in human serum which are involved in the immune response, including immunoglobin (IgG), interleukin-Ibeta (IL-IP), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-13 (IL-13), interferon-gamma (lEN-y) and tumor necrosis factor-alpha (TNF-a). 

The toxicity of TSST-1 and HI 35 A was tested in 20 g BALB/c mice (n=15 per dose) injected intraperitoneally (ip) with either protein diluted in PBS. Four hours later, mice were injected ip with 75 pg of E. coli 055 B5 LPS (Difco Laboratories, MI) and lethality was observed over 72 h. The serum cytokine levels of tumor necrosis factor a and P (TNF), as well as interferon gamma (IFNy), were measured over 14 h (2 h intervals) in mice injected with either 15 pg TSST-1, 15 pg TSST-1 plus 75 pgLPS, 15 pgH135Aplus LPS, or 75 pg LPS only. Serum levels of TNF were determined by an ELISA (Genzyme, M A) with triplicate samples the standard deviation (SD). Data for IFNy were collected from an L929 cell lysis assay with duplicate samples 10%. 

In 1975, Carswell et al. discovered that this bacterial-induced tumor killing activity could he transferred from one animal to another. When the serum of a mouse that is pretreated with LPS (also called endotoxin) is injected into another animal that has not been treated with endotoxin but harbors a transplantable skin tumor, the tumor undergoes necrosis. In addition, Carswell etal. also showed that addition of this substance (which they dubbed tum<.)r necrosis factor, or TNF) to cultures of transformed cells results in death of the cells (Helson ec al., 1975). It is now known that TNF is a member of a class of proteins called cytokines, which are immune hormones, that is, proteins that are secreted by certain immune cells during stimulation. These proteins are extraordinarily important in the immune response, by acting as the messengers between different cells to relay information (Abbas, 1991). 

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