Inflammation biomarker

The so-called COX (cyclooxygenase) inhibitors are widely applied in the treatment of acute and chronic pain and inflammation, that is, in rheumatoid arthritis and osteoarthritis. The characterization of the correlation between the plasma concentration of COX inhibitors and their pain- and inflammation-decreasing ability is often done via inflammation biomarkers such as PGE2 and thromboxane B2. 

Our new appreciation of the role of inflammation in atherosclerosis shows the way for translation of these novel biological insights to clinical practice, for example by aiding the identification of individuals at risk of adverse cardiovascular events [5]. In this context, inflammatory biomarkers such as CRP merit rigorous consideration for inclusion in risk assessment strategies. In addition, these scientific advances provide a framework... 

Biomarkers of sepsis have been controversial. The routine use of endotoxin, procalcitonin, or other markers is not routinely recommend. Concentrations of procalcitonin in serum are usually increased in sepsis, but fail to differentiate between infection and inflammation. However, procalcitonin has a high negative predictive value and could allow for the discontinuation of antibiotics. 

A number of commercial antibody-based microarrays for multiplexed cytokines analysis are now available (Beckman Coulter BD Biosciences Panom-ics Pierce S S Zyomyx and others). Cytokines are essentially biomarkers of cell injury, inflammation, and apoptosis. They are released by cells in culture in response to drug action (Turtinen et al., 2004) or are elevated in serum in various disease states. Moreover, numerous cytokines are involved in cellular response and many serve as dual effectors (Asao and Fu, 2000). As a result, anticytokine microarrays are being evaluated in drug discovery for off-target toxicity testing to replace standard ELISA plate formats. 

Mathur, S., Devaraj, S., Grundy, S.M., and Jialal, L, Cocoa products decrease low density lipoprotein oxidative susceptibility but do not affect biomarkers of inflammation in humans, J. Nutr., 132, 3663, 2002. 

It is known that chronic active inflammation in the gastric mucosa involves several interleukins (IL-8, IL-10 and IFN-gamma) known as immunological markers of the blood serum [33]. Hence it is possible that extensive gastric inflammation would lead to an increased release of some of the volatile inflammatory biomarkers in breath causing differences in the sensor response. 

Xu J, Lowey J, Wiklund F etal. The interaction of four genes in the inflammation pathway significantly predicts prostate cancer risk. Cancer Epidemiol Biomarkers Prev 2005, 14-2563-256S. 

Inflammation is an important factor in the development of cardiovascular disease. Most clinical studies involving inflammation parameters have been relatively small. The Nurses Health Study involving 727 women was the largest study designed to determine the effects of n-3 fatty acids on biomarkers of inflammation and endothelium activation (Lopez-Garcia et al., 2004). They found an inverse association between ALA intake and plasma concentrations of C-reactive protein (a marker for inflammation), Interlukin-6, and E-selectin. Bemelmans et al. (2004) also found an inverse association between C-reactive protein and ALA intake in a randomized, double-blind placebo-controlled study involving 103 hypercholesterolemic subjects. 

Lopez-Garcia, E., Schulze, M.B., and Manson, J.A.E. 2004. Consumption of (n-3) fatty acids is related to plasma biomarkers of inflammation and endothelial activation in women. J. Nutr. 134, 1806-1811. 

Atherosclerosis including acute coronary syndromes is an inflammatory process (37). Among biomarkers of inflammation, most attention and data has focused on C-reactive protein (CRP), which have been reported to be independently related to risk of future CHD events (38), Moreover, in the PROVE-IT TIMI 22 study, CRP levels at 30 days after treat-ment were not only independent of LDL cholesterol levels at that time but outcomes were improved in those who achieved not only an LDL cholesterol level of < 70 mg/dL (l.8mmol/L) but also CRP levels less than 2mg/L (39), However, uncertainties still remain and at this time it is considered premature to include CRP levels as a specific target,... 

Plasma and urine samples from atherosclerotic and control rats were comparatively analyzed by ultrafast liquid chromatography coupled with ion trap-time-of-flight (IT-TOF) MS (UFLC-IT/TOF-MS) (16). They identified 12 metabolites in rat plasma and 8 metabolites in rat urine as potential biomarkers. Concentrations of leucine, phenylalanine, tryptophan, acetylcar-nitine, butyrylcamitine, propionylcamitine, and spermine in plasma and 3-0-methyl-dopa, ethyl /V2-acety I -1. -argininate, leucylproline, glucuronate, A(6)-(A-threonylcarbonyl)-adenosine, and methyl-hippuric acid in urine were decreased in atherosclerosis rats ursodeoxycholic acid, chenodeoxycholic acid, LPC (06 0), LPC (08 0), and LPC (08 1) in plasma and hippuric acid in urine were increased in atherosclerosis rats. The altered metabolites demonstrated abnormal metabolism of phenylalanine, tryptophan, bile acids, and amino acids. Lysophosphatidylcholine (LPC) plays an important role in inflammation and cell proliferation, which shows a relationship between LPC in the progress of atherosclerosis and other inflammatory diseases. 

MPs (also called microvesicles) are present in the blood of healthy individuals and are increased in various diseases including CVD. They are small membrane vesicles derived from activated and apoptotic cells. Importantly, MPs have been proposed to play roles in thrombosis, inflammation, and angiogenesis (103). MPs are also released in the circulation (104), and ever since their potent procoagulatory properties were first recognized in the field of homeostasis (105), the interest in their potential pathophysiological importance has increased (106). MP metabolome may be a useful and reliable source of biologically relevant disease biomarkers. 

R. P. F. Schins, D. Polat, J. Begerow, M. Turfeld, A. Becker, P. J. A. Borm, Platinum levels in nasal lavage Buid as a biomarker for traffic-related exposure and inflammation in children, Sci. Total Environ., 334D335 (2004), 447D445. 

The usual GLP 30- or 60-day repeat-dose toxicology study with a recovery group offers an opportunity to perform a more systematic investigation of the more subtle pharmacodynamic or toxicologic effects of biopharmaceuticals than those endpoints usually incorporated into such protocols. Some of these demand tissue samples, but many involve noninvasive biomarkers that can be carried forward into early phase human studies. These might include CNS assessments, inflammation and immune activation or suppression, cell proliferation or apoptosis in tissue samples, and end-organ toxicities. 

Pentraxins as a key component on innate immunity, Cum Opin. Immunol. 18,10-15,2006 Vidt, D.G., Inflammation in renal disease. Am. J. Cardiol. 97, 20A-27A, 2006 Armstrong, E.J., Morrow, D.A., and Sabatine, M.S., Inflammatory biomarkers in acute coronary syndromes. Part 11 acute-phase reactants and biomarkers of endothelial cell activation. Circulation 113, el52-el55, 2006. See also Heat-Shock Proteins. 

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