Endotoxemia

TNF is produced and secreted by activated cells within minutes following contact with LPS, reaching peak levels at 90-120 minutes after the admnistration of Escherichia coli endotoxin in human volunteers (M27). Van Deventer et al. (D15) could not detect serum TNF levels during experimental endotoxemia. Even during continuous intravenous administration of recombinant TNF (rTNF), serum TNF rapidly becomes undetectable (M27). It has been proposed that circulating soluble TNF receptors (sTNF-Rs) may be an important down-regulating mechanism (G10). 

Chlorpromazine (CPZ) and pentoxifylline (PTX) were shown to inhibit TNF release and improve survival during murine endotoxemia (Gl). CPZ (M25) and epinephrine (PI6) pretreatment markedly up-regulated IL-10 production induced by LPS, a phenomenon also observed with cyclosporine (Dl). PTX pretreatment did not affect LPS-induced IL-10 release. Thus, TNF and IL-10 can be differentially regulated during murine endotoxemia. The sustained or even increased production of IL-10 could play a role in the protective effects of these drugs against LPS toxicity in vivo. 

Following trauma, sepsis, or endotoxemia, a marked decrease in t-PA and increases in PAIs, more pronounced in nonsurvivors, have been noted (H20). An-... 

Relatively few data are available on the response of ANP to endotoxemia or septic shock. In an ovine model, a 13-fold increase in blood ANP concentration has been found 2 hours after endotoxin administration in a dose of 1.5 pg/kg body weight (LI7). The ANP level remained elevated during the first 6 hours and was associated with marked diuresis and natriuresis and with decreased cardiac output and increased peripheral resistence (LI7). In human studies, a significantly higher ANP blood level was observed in ARDS (E4) and in patients with acute respiratory failure associated with sepsis (M30). In a longitudinal study, we found that plasma ANP levels were increased in patients with sepsis, but the ANP levels showed no relation to the severity of disease or to the presence of shock (B8). 

G8. Gerard, C., Bruyns, C., Marchant, A., Abramowicz, D Vandenabeele, P Delvaux, A., Fiers, W Goldman, M., and Velu, T., Interleukin-10 reduces the release of tumor necrosis factor and prevents lethality in experimental endotoxemia. J. Exp.Med. 177,547-550 (1993). 

H20. Herbertson, M. J., Werner, H. A., and Walley, K. R., Nitric oxide synthase inhibition partially prevents decreased LV contractility during endotoxemia. Am. J. Physiol. 270, HI979-HI984 (1996). 

L17. Lubbesmeyer, H. J., Woodson, L., Traber, L. D., Flynn, J. T., Herndon, D. N., andTraber, D. L., Immunoreactive atrial natriuretic factor is increased in ovine model of endotoxemia. Am. J. Physiol. 254, R567-R571 (1988). 

P17. van der Poll, T., Levi, M Van Deventer, S. J., Ten Cate, H., Haagmans, B. L., Biemond, B. J., Buller, H. R Hack, C. E., and Ten Cate, J. W., Differential effects of anti-tumor necrosis factor monoclonal antibodies on systemic inflammatory responses in experimental endotoxemia in chimpanzees. Blood 83,446-451 (1994). 

Ahmad, N. et al., Inhibition of macrophages with gadolinium chloride alters intercellular adhesion molecule-1 expression in the liver during acute endotoxemia in rats, Hepatology, 29, 728, 1999. 

Wizemann, T.M. et al., Production of nitric oxide and peroxynitrite in the lung during acute endotoxemia, J. Leukoc. Biol., 56, 759, 1994. 

Gardner, C.R., Laskin, J.D., and Laskin, D.L., Distinct biochemical responses of hepatic macrophages and endothelial cells to platelet-activating factor during endotoxemia, J. Leukoc. Biol., 57, 269, 1995. 

Rossignol DP, Lynn M. (2005) TLR4 antagonists for endotoxemia and beyond. Curr Opin Invest Drugs 6 496-502. 

Hsu, D. Z., and M. Y. Liu. Sesame oil attenuates multiple organ failure and increases survival rate during endotoxemia in rats. Critic Care Med... 

Endotoxemia correlates with severity of gram-negative sepsis. Nowadays, one of the recognized effective treatment methods is the use of Polymyxin B, which links and inactivates EPS both in a bacterinm wall and in a free form, however its... 

Hanasawa K, Tani T, Oka T, Kodama M (1984) A new treatment for endotoxemia with direct hemoperfusion by polymyxin-immobilized fiber. Artif Organs 8(3) 397-398... 

The assessment of basic hematological indicators and endotoxemia blood indices such as creatinine, urea and bilirubin in patients treated by standard hemosorption procedure revealed the insufficiency of its detoxification effect. Only after three hemosorption sessions (HS) were positive clinical dynamics and reduction of endotoxemia indices seen in patients of the control group, hi the treatment group... 

Rodent KC and HC, as well as human HC, express an inducible NO synthase under septic or inflammatory conditions. In vivo in endotoxemia, this expression is transient. Our in vivo data indicate that this induced -NO serves a protective role in the liver and reduces hepatic injury in endotoxemia. This protective action may be mediated by the capacity of NO to neutralize oxygen radicals and prevent platelet adherence and aggregation. Our in vitro studies show that HC-derived -NO can activate soluble guanylate cyclase. Other in vitro effects include the nonspecific suppression of protein synthesis and a small reduction in mitochondrial aconitase activity. The relevance of these in vitro actions to hepatic function in vivo remains to be determined. 

Phenylbutazone, the major suxibuzone metabolite, has been approved by the FDA for use in dogs and horses (87). It is not licensed in cattle but its properties make it useful in this species for the treatment of musculoskeletal conditions, mastitis, endotoxemia, and castration. Since there is evidence of extralabel use for treatment of mastitis in lactating cows, residues of this drug may be found in bovine milk. 

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