Interleukins injury

These proteins are called acute phase proteins (or reactants) and include C-reactive protein (CRP, so-named because it reacts with the C polysaccharide of pneumococci), ai-antitrypsin, haptoglobin, aj-acid glycoprotein, and fibrinogen. The elevations of the levels of these proteins vary from as little as 50% to as much as 1000-fold in the case of CRP. Their levels are also usually elevated during chronic inflammatory states and in patients with cancer. These proteins are believed to play a role in the body s response to inflammation. For example, C-reactive protein can stimulate the classic complement pathway, and ai-antitrypsin can neutralize certain proteases released during the acute inflammatory state. CRP is used as a marker of tissue injury, infection, and inflammation, and there is considerable interest in its use as a predictor of certain types of cardiovascular conditions secondary to atherosclerosis. Interleukin-1 (IL-1), a polypeptide released from mononuclear phagocytic cells, is the principal—but not the sole—stimulator of the synthesis of the majority of acute phase reactants by hepatocytes. Additional molecules such as IL-6 are involved, and they as well as IL-1 appear to work at the level of gene transcription. 

Sekido N, Mukaida N, Harada A, Nakanishi I, Watanabe I, Matsushima K. Prevention of lung perfusion injury in rabbits by a monoclonal antibody against interleukin-8. Nature 1993 365 654-657. 

Boyle EM, Jr., Kovacich JC, Hebert CA, et al. Inhibition of interleukin-8 blocks myocardial ischemia-reperfusion injury. J Thorac Cardiovasc Surg 1998 116(1) 114-121. 

Many extracellular agents or inducers of cell injury or stress such as tumor necrosis factor alpha (TNFa), fas ligands, Y-interferon, interleukin-1... 

Endotoxicity results from the interaction of a bacterial cell envelope component (e.g., LPS or PG with a cell surface receptor constituting part of the nonspecific immune system, (i.e., a toll-like receptor on white blood cells). This results in the production of cytokines [e.g., interleukin 1 (IL-1) or tumor necrosis factor (TNF)] as part of an intracellular enzyme cascade which can cause severe tissue injury. Bioassays or immunoassays can be used to detect such reactions respectively. As noted above the most widely used bioassay is the LAL assay. A lysate of amoebo-cytes of the horseshoe crab (Limulus) contains an enzymatic clotting cascade which is activated by extremely low levels of LPS (nanogram levels or lower). There are variants of this assay that can detect PG, but they are not as widely used. As noted above, other bioassays employ cultured cell lines that respond to LPS or PG, respectively. Unfortunately bioassays are highly amenable to false positives (from the presence of cross-reactive substances) or false negatives from inhibition (by contaminants present in the sample) [10]. A detailed discussion of these assays is beyond the scope of this chapter and has been reviewed elsewhere [1]. 

Dinarello CA. Interleukin-1 is produced in response to infection and injury. Rev infect Dis... 

Interleukin-1 (11-1) plays a key role in the body s response to microbes and to tissue injury.210,211 It actually consists of three similar proteins, Il-la, IL-1 5, and 11-1 receptor antagonist. The first two are the active cytokines with a wide range of effects among... 

Sawa, Y., Ichikawa, H., Kagisaki, K., Ohata, T., and Matsuda, H., Interleukin-6 derived from hypoxic myocytes promotes neutrophil-mediated reperfusion injury in myocardium. J. Thorac. Cardiovasc. Surg. 116, 511-517 (1998). 

Kleinschnitz, C., Hofstetter, H. H., Meuth, S. G., Braeuninger, S., Sommer, C., and Stoll, G. (2006). T cell infiltration after chronic constriction injury of mouse sciatic nerve is associated with interleukin-17 expression. Exp. Neurol. 200, 480-485. 

Friedlander, R. M., Gagliurdini, V., Hara, H., Fink, K. B., Li, W., MacDon-old, G., Fishman, M. C., Greenberg, A. H., Moskowitz, M. A., Yuan,J., (1997). Expression of a dominant negative mutant of interleukin-1 (3 converting enzyme in transgenic mice prevents neuronal cell death induced by trophic factor withdrawal and ischemic brain injury.. Exp. Med. 185, 933—940. 

Goss J. R., Styren S. D., Miller P. D., et al. (1995) Hypothermia attenuates the normal increase in interleukin 1 beta RNA and nerve growth factor following traumatic brain injury in the rat. J. Neurotrauma 12, 159-167. 

Kinoshita K., Chatzipanteli K., Vitarbo E., Truettner J. S., Alonso O. F., and Dietrich W. D. (2002) Interleukin-1 beta messenger ribonucleic acid and protein levels after fluid-percussion brain injury in rats importance of injury severity and brain temperature. Neurosurgery 51, 195-203 discussion 203. 

Kline A. E., Bolinger B. D., Kochanek P. M., et al. (2002) Acute systemic administration of interleukin-10 suppresses the beneficial effects of moderate hypothermia following traumatic brain injury in rats. Brain Res. 937, 22-31. 

McClain C.J., Cohen D.,OttL.,DinarelloC. A., and Young B. (1987) Ventricular fluid interleukin-1 activity inpatients with head injury. 7. Lab. Clin. Med. 110,48-54. 

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