Protein acute phase

A number of adipokines are linked to inflammation and immunity (Fig. 1). This includes both leptin and adiponectin, and also a number of other key inflammatory proteins, particularly cytokines and chemokines [1]. The cytokines and chemokines encompass interleukin-1(3 (EL-1 (3), IL-6, DL-10, TNFa, monocyte chemoattractant protein-1 (MCP-1), and macrophage migration inhibitory factor (MIF). Other major inflammation-related adipokines include nerve growth factor (NGF), and acute phase proteins such as serum amyloid A and haptoglobin. In addition, adipocytes secrete plasminogen activator inhibitor-1 (PAI-1), which is an important thrombotic factor as well as an acute phase protein. 

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. 

Gabay C, Kushner I Acute-phase proteins and other systemic responses to inflammation. New Engl J Med 1999 340 448. 

The serum concentration of a number of proteins increases dramatically during infection. Their levels can increase by up to 100-fold compared with normal levels. They are known collectively as acute phase proteins and certain of them have been shown to enhance phagocytosis in conjunction with complement. 

NF-xB activates genes encoding MHC class I antigens, IL-1, TNFa, IL-6, the interleukin-2 (IL-2) receptor, some acute-phase proteins and the adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) (lademarco... 

Copper salts such as CuS04 are potent catalysts of the oxidative modification of LDL in vitro (Esterbauer et al., 1990), although more than 95% of the copper in human serum is bound to caeruloplasmin. Cp is an acute-phase protein and a potent inhibitor of lipid peroxidation, but is susceptible to both proteolytic and oxidative attack with the consequent release of catalytic copper ions capable of inducing lipid peroxidation (Winyard and... 

Laurell, C.B. (1985). Acute phase proteins - a group of protective proteins. In Recent Advances in Clinical Biochemistry , No. 3 (eds. C.P. Price and K.G.M.M. Alberti) pp. 103-124. Churchill Livingstone, Edinburgh. 

Solerte, S.B., Adamo, S., Viola, C., Schianca, G.P.C., Crippa, A. and Ferrari, E. (1984). Acute-phase protein reactants pattern and macroglubulin in diabetes mellitus. Pathophysiological aspects in diabetic microangiopathy. Ric. Clin. Lab. 14, 575-579. 

IL-1 (17.5) Monocyte/macrophage, lymphocyte, neutrophil, endothelium, fibroblast keratinocyte Activation of T cells, B cells, natural killer cells, osteoblasts, and endothelium. Induces fever, sleep, anorexia, ACTH release, hepatic acute phase protein synthesis and HSPs. Leads to myocardial depression, hypercoagulability, hypotension/sbock, and death. Simulates production of TNF, IL-6, and IL-8 and stress hormone release. Suppression of cytochrome P-450, thyro-globulin, and lipoprotein synthesis. Procoagulant activity. Antiviral activity. 

L4. Le, J., and Vilcek, J., Interleukin 6, a multifunctional cytokine regulating immune reactions and the acute phase protein response. Lab. Invest. 61,588-602 (1989). 

It has been well documented that the anaemia of chronic disease, ACD, results in a lowering of various haematological parameters. Several mediators are involved, among them histamine, serotonin, bradykinin, prostaglandins and, as found more recently, cytokines and nitric oxide. ACD is a parameter of systemic autoimmune disorders. The severe inflammatory stimuli lead to several systemic changes, mediated by inflammation-associated cytokines, e.g. IL-6, IL-1 TNFa, TGF beta that regulate hepatic synthesis of the acute phase proteins. 

Sironi L et al. Acute-phase proteins before cerebral ischemia in stroke-prone rats identification by proteomics. Stroke 2001 32 753-760. 

Rat Organic versus conventionally grown wheat, fed at well-nourished or protein-energy-malnourished levels In vitro lymphocyte proliferation response and acute phase proteins not different between organic and conventional wheat when fed at well nourished or protein-energy-malnourished levels. (Finamore et al., 2004)... 

Along with IL-6, it induces synthesis of acute-phase proteins in hepatocytes. 

Shima, M. and Adachi, M., Effects of environmental tobacco smoke on serum levels of acute phase proteins in schoolchildren, Prev. Med. 25, 5, 617, 1996. 

As reviewed by Ryffel (1996) most side effects in humans of a therapy with rDNA therapy may be predicted by data from experimental toxicology studies, but there are exceptions. IL-6 for example, induced a sustained increase in blood platelets and acute phase proteins, with no increase in body temperature. In human trials, however, there were increases in temperature. 

The precise function of many acute-phase proteins is not known. C-reactive protein binds lipids, whilst a-macroglobulin and ceruloplasmin can scavenge some reactive oxygen metabolites. However, many acute-phase proteins are glycoproteins and can bind to bacterial surfaces hence, they may serve as non-specific opsonins for phagocytosis, and their synthesis is stimulated by IL-1 and IL-6. 

IL-6 induces terminal maturation of B cells, promotes the growth of hy-bridoma/myeloma cells and T cells, and acts upon haematopoietic progenitors in synergy with IL-1 and IL-3. It also induces the production of acute-phase proteins by liver cells. In addition to its production by neutrophils, IL-6 is also synthesised by monocytes, T and B cells, fibroblasts, cardiac myxoma cells, some bladder carcinomas, cervical cancer cells and glioblastomas. Stimulated neutrophils generate about ten times less IL-6 (on a per-cell basis) than do monocytes. 

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