Interleukin elevated

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. 

Fever is the most common manifestation. The thermoregulatory centre in the hypothalamus regulates body temperature and this can be affected by endotoxins (heat-stable lipopolysaccharides) of Gram-negative bacteria and also by a monokine secreted by monocytes and macrophages called interleukin-1 (IL-1) which is also termed endogenous pyrogen. Antibody production and T-cell proliferation have been shown to be enhanced at elevated body temperatures and thus are beneficial effects of fever. 

Because of the multiple degradation pathways that may take place at elevated temperature, protein stability monitoring data may not conform to the Arrhenius relationship, and the maximum temperature selected for accelerated stability studies must be carefully selected. Gu et al. [32] described the different mechanisms of inactivation of interleukin-1 (3 (IL-1 (3) in solution above and below 39°C. In this example, the multiple mechanisms precluded the prediction of formulation shelf life from accelerated temperature data. In contrast, by working at 40° C and lower, Perlman and Nguyen [33] were able to successfully extrapolate data from stability studies of tissue plasminogen activator down to 5°C. 

Watson and Kenney [62] describe the use of high-performance size-exclusion chromatography to examine the aggregation of interferon-y and interleukin-2 after storage at elevated temperature, after mechanical agitation, and following rapid freeze-thaw. An excellent review on SEC can be found in Ref. 63. 

The coupling of superantigen—major histocompatibility complex class II to T-cell receptor swifdy results in cell-signaling cascades. ° These staphylococcal toxins can increase levels of phosphatidyl inositol from quiescent T cells, such as other mitogens, as well as elicit intracellular Ca movement that activates the protein kinase C (PKC) pathway important for interleukin-2 (IL-2) expression. " IL-2 is intimately linked to T-cell proliferation. In addition to the PKC pathway, the protein tyrosine kinase (PTK) pathway is also activated by superantigens, leading to elevated expression of various proinflammatory cytokines. Staphylococcal superantigens also potently activate transcriptional factors NF-/IB (nuclear factor kappa B) and AP-1 (activator protein-1), which subsequently elicit the synthesis of proinflammatory cytokines. " " ... 

Pyrogens (e.g., bacterial matter) elevate—probably through mediation by prostaglandins (p. 196) and interleukin-1—the set point of the hypothalamic temperature controller (B2). The body responds by restricting heat loss (cutaneous vasoconstriction chills) and by elevating heat production (shivering), in order to adjust to the new set point (fever). Antipyretics such as acetaminophen and ASA (p. 198) return the set point to its normal level (B2) and thus bring about a defervescence. 

Yarim GF, Karahan S, Nisbet C (2007) Elevated plasma levels of interleukin 1 beta, tumour necrosis factor alpha and monocyte chemotac-tic protein 1 are associated with pregnancy toxaemia in ewes. Vet Res Commun 31 565-573... 

Chavali, S. R., W. W. Zhong, T. Utsunomiya, and R. A. Forse. Decreased production of interleukin-1-beta, pros-taglandin-E2 and thromboxane-B2, and elevated levels of interleukin-6 and -10 are associated with increased survival during endotoxic shock in mice consuming diets enriched with sesame seed oil supplemented with Quil-A saponin. Int Arch Allergy Immunol 1997 114(2) 153-160. 

Greist JH, Jenike MA, Robinson DS, et al Efficacy of fluvoxamine in obsessive-compulsive disorder results of a multicentre, double-bhnd, placebo-controlled trial. European Journal of Clinical Research 7 195-204, 1995c Griffin WST, Stanley LC, Ling C, et al Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. Proc Natl Acad Sci U S A 86 7611-7615, 1989... 

Bohlen H, Kessler M, Sextro M et al. Poor clinical outcome of patients with Hodgkin s disease and elevated interleukin-10 serum levels clinical signiflcance of interleukin-10 serum levels for Hodgkin s disease. Ann Hematol 2000 79 110-113. 

Sarris AH, Kliche KO, Pethambaram P et al. Interleukin-10 levels are often elevated in serum of adults with Hodgkin s disease and are associated with inferior failure-free survival. Ann Oncol 1999 10 433 40. 

Yawalkar N, Hari Y, Helbing A, von Greyerz S, Kappeler A, Baathen LR, Pichler WJ. Elevated serum levels of interleukins 5, 6, and 10 in a patient with drug-induced exanthem caused by systemic corticosteroids. J Am Acad Dermatol 1998 39(5 Part l) 790-3. 

Harris TB, Ferrucci L, Tracy RP, Corti MC, Wacholder S, Ettinger WH Jr, Heimovitz H, Cohen HJ, Wallace R. Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. Am J Med 1999 106 506-512. 

There is emerging evidence that OSA may be a pro-inflammatory disorder with elevated circulating cytokines [60]. Abdominal visceral fat is a major reservoir of cytokines, and obesity is a leading risk factor for the presence of OSA [60], The mechanism(s) whereby pro-inflammatory cytokines are elevated in OSA is not fully elucidated, but may be related to the excessive sympathetic nervous system activation notable in OSA. Tumor necrosis factor (TNF)-a and interleukin (IL)-6 levels are elevated in OSA [61,62] and the circadian rhythm of TNF-a is disrupted in OSA [63]. IL-6 levels are higher again in OSA patients with systemic hypertension compared to normotensive apneics [60], IL-6 levels return to normal in OSA patients treated effectively with CPAP [64]. Other mediators of inflammation elevated in OSA include intercellular adhesion molecule-1 and C-reactive protein, the latter being synthesized primarily in hepatocytes in response to IL-6 [60], The presence of these and other pro-inflammatory cytokines may link to the increased prevalence of cardiovascular morbidity in OSA. 

Yokoe T, Minoguchi K, Matsuo H, Oda N, Minoguchi H, Yoshino G, Hirano T, Adachi M (2003) Elevated levels of C-reactive protein and interleukin-6 in patients with obstructive sleep apnea syndrome are decreased by nasal continuous positive airway pressure. 

M8. Matsumoto, K., and Kanmatsuse, K., Elevated interleukin-18 levels in the urine of nephrotic patients. Nephron 88, 334-339 (2001). 

Lll. Leser, H. G., Gross, V., Scheibenbogen, C., Heinisch, A., Salm, R., Lausen, M., Ruckauer, K., Andreesen, R., Farthmann, E. H., and Scholmerich, J., Elevation of serum interleukin-6 concentration precedes acute-phase response and reflects severity in acute pancreatitis. Gastroenterology 101, 782-785 (1991). 

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