Endotoxin cytokines

Cytokines, endotoxin, A growth factors, tumor promotors... 

The circumstances of the release, and the actions, of the endothelins are extensive. It was originally discovered that endothelin has profound vasoconstrictor actions, and was released particularly in anoxia, so a role in all varieties of vasospastic disease or hypertension has long been suspected. Other stimuli for production by the endothelium (which occurs at the transcriptional level, since the endothelium has no storage vesicles) are believed to include shear forces, some cytokines, endotoxin, thrombin, growth factors and a... 

NF-xB is a pleiotropic transcription factor that responds rapidly to a variety of stimuli including cytokines, endotoxin and oxidative stress. NF-xB controls both cell... 

Two isoforms of COX have been described, which are here referred to as COX-1 and COX-2. COX-1 is a constitutive enzyme with a role in basal or housekeeping prostaglandin synthesis, whereas COX-2 is an inducible enzyme, which is associated with inflammatory processes. COX-2 is strongly induced by pro-inflammatory or mitogenic agents such as cytokines, endotoxins, tumour promoters, mitogens and lipids. Both isoforms have similar and values for... 

Cell activation/culture etc. Free from cytokines, endotoxin, preservative, etc. >80%... 

Interleukin-1 OC and (3. IL-1 has radioprotective activity toward BM and other tissues (151,164). IL-1 is produced in response to endotoxin, other cytokines, and microbial and viral agents, primarily by monocytes and macrophages. Other nucleated cells can also produce it. IL-1 appears to play an important role in the regulation of normal hemopoiesis directly by stimulating the most primitive stem cells and indirectly by stimulating other hemopoietic factors, including G-CSF, GM-CSF, M-CSF, and IL-6. 

There are two isoforms of COX in animals COX-1 (figure a), which carries out normal, physiological production of prostaglandins, and COX-2 (figure b), which is induced by cytokines, mitogens, and endotoxins in inflammatory cells and is responsible for the production of prostaglandins in inflammation. 

Bacterial products such as lipopolysaccharides (endotoxins) and cytokines (IL-2) are able to activate the contact system in vitro and in vivo (D9, H4, H7, M41). Immediately after severe trauma or after surgical intervention and particularly during sepsis, a reduction of plasma contact system proteins has been found (C10, K1, N9). Gel filtration studies of plasma demonstrated that plasma PK after activation becomes complexed with a2-M and Cl-Inh (W4). These complexes are rapidly eliminated from the circulation in vivo. In experimental studies in which pulmonary insufficiency was induced in dogs, a significant reduction of plasma kallikrein inhibitors was observed together with reduced HMK. Analysis of the relation be-... 

Cl 2, Casey, L. C., Balk, R. A., and Bone, R, C., Plasma cytokine and endotoxin levels correlate with survival in patients with the sepsis syndrome. Ann. Intent. Med. 119,771-778 (1993). 

E7. Endo, S., Inada, K., Inoue, Y., Kuwata, Y Suzuki, M., Yamashita, H., Hoshi, S and Yoshida, M T vo types of septic shock classified by the plasma levels of cytokines and endotoxin. Circ. Shock 38,264-274(1992). 

M9. Marchant, A., Bruyns, C., Vandenabeele, P., Abramowicz, D., Gerard, C Delvaux, A., Ghezzi, P., Velu, T., and Goldman, M Interleukin-10 differentially regulates cytokine production during murine endotoxin shock. 33rd Interscience Conference on Antimicrobial Agent and Chemotherapy, New Orleans, 12 (Abst) (1993). 

Another issue of relevance is that certain biopharmaceuticals (e.g. cytokines such as 1L-1 and TNF Chapter 9) themselves induce a natural pyrogenic response. This rules out use of the rabbit-based assay for detection of exogenous pyrogens in such products. Such difficulties have led to the increased use of an in vitro assay the Limulus ameobocyte lysate (LAL) test. This is based upon endotoxin-stimulated coagulation of amoebocyte lysate obtained from horseshoe crabs. This test is now the most widely used assay for the detection of endotoxins in biopharmaceutical and other pharmaceutical preparations. 

Early research showed that Pb exposure could increase sensitivity to bacterially-derived endotoxins [63] as well as increase production of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-a) by macrophages [64-67], Studies in several species indicate that Pb boosts production of TNF-a both immediately following adult exposure and in later life following gestational exposure. Flohe and coworkers [67] reported that Pb-induced elevation in TNF-a production is sensitive to both protein kinase C signaling as well as protein production. Not only can the production of TNF-a be elevated following exposure to Pb, but also the expression of the receptor for TNF-a (TNF-R) is elevated [68], Therefore, the combined effect of elevated cytokine production by macrophages as well as increased receptor expression would be expected to contribute to problematic inflammatory responses. 

LPS, the immunoactive component of endotoxin, is a constituent of the outer membrane of Gram-negative bacterial cell walls. LPS is found in the environment and has been extensively studied, both as a mediator of inflammation and as a major contributing factor to bacterial pathogenesis.60 LPS exerts many of its effects through induction of pro-inflammatory cytokines, including IL-ip, TNF-a and IL-6.61 An important feature... 

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