Acute phase reactant

Acute phase reactants (e.g., C-reactive protein) are proteins that increase during inflammation and are deposited in damaged tissues. They were first discovered in the serum, but are now known to be involved in inflammatory processes in the brain (e.g., found in the brain of Alzheimer patients and associated with amyloid plaques). 

An acute-phase reactant protein, the plasma concentration of which increases in inflammatory states. 

One of the questions confronting investigators in the HS field is whether fever or other acute phase reactants can induce HS gene expression. In vitro studies utilize extraordinary temperatures of 42 °C and higher. Core body temperatures may approach 40 °C as a result of fever. In most in vitro systems, this temperature does not lead to the HS response. However, there are reports that fever induces the increased synthesis of hsps in peripheral blood lymphocytes (Ciavarra, 1990). This response was observed in mononuclear cells exposed to febrile temperatures and in cells isolated from a medical intern who developed fever. 

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. 

Shirley, NY) sodium ferric gluconate (Ferrlecit by Watson Pharmaceuticals, Inc., Corona, CA) and iron sucrose (Venofer by American Reagent, Inc., Shirley, NY). Initiation of IV iron should be based on evaluation of iron stores. A serum ferritin level less than 100 ng/mL in conjunction with a TSAT level less than 20% indicates absolute iron deficiency and is a clear indication for the need for iron replacement.31 When TSAT is less than 20% in conjunction with normal or elevated serum ferritin levels, treatment should be based on the clinical picture of the patient, as serum ferritin is an acute phase reactant, which may become elevated with inflammation and stress. Iron supplementation may be indicated if Hgb levels are below the goal level. 

Acute phase reactants tumour necrosis factor-a, interleukin-6 and -8,... 

Although normally present in normal human plasma in abundance ( 0.6 mg/ml, 10 pM) (27-30), concentrations ofhemopexin are sensitive to a variety of pathological conditions. Decreased levels have been noted in chronic and severe hemolytic states (31) and in heme infusion of acute intermittent porphyria patients (32). On the other hand, hemopexin levels increase in the acute-phase response (33-36), and hemopexin has been designated as a type II acute-phase reactant. Plasma hemopexin also increases in certain conditions of muscle breakdown and neuromuscular disease (37). 

In patients with lymphocytic CSF cytological syndromes, elevation of CSF C4 concentrations was observed. Leakage of several proteins across the blood-CSF barrier was also found. Leakage of C4 complement into CSF depends on the functional state of the barrier to a certain extent, being partially selective. Under pathological circumstances, the rate of penetration of protein fractions across the blood-CSF barrier can be modified selectively, which has been proved in CSF acute-phase reactants. They are highly influenced by the production of cytokines. These considerations evoke the question as to whether similar mechanisms of penetration can be expected in cytokines. Elucidation of the pharmacokinetics of interferons in CSF could substantially influence our approach not only to MS patients but to others as well (A18). 

Antithrombin HI in cerebrospinal fluid can be easily denoted as an inflammatory marker. Correlations with levels of immunoglobulins, their intrathecal oligo-clonal synthesis, complement components, and acute-phase reactants confirm such concepts. Correlations with apolipoproteins and with the presence of lipophagic macrophages in cytological preparations confirm the elevation of CSF AT III levels when a destructive lesion of the CNS is present. 

Tetranectin (TN). Tetranectin is a plasma protein of about 80 kDa. A reduction in the serum TN level has been described in malignant disease and in other conditions with tissue remodeling, whereas it does not seem to exhibit acute-phase reactant behavior. Using a polyclonal ELISA to determine the TN concentrations in pair of CSF/serum quotient in pair of CSE and serum, it was found that the CSE/serum quotient compared to the QAib was compatible with intrathecal TN synthesis. In clinically definite multiple sclerosis a reduced CSF/serum quotient was found, suggesting that the hypothesis of a reduced TN level as a marker of tissue remodeling may be extended to the CNS (C5). 

Rheumatoid arthritis—Decreased acute phase reactants (ESR, C-reactive protein), pain relief, reduction in number of swollen joints, improved range of motion, less fatigue, greater functional capacity, less structural damage, maintenance of normal lifestyle... 

Rfieumatoid artfiritis Tender, swollen joints, visual analogue scale for pain acute phase reactants (ESR,C-reactive protein), duration of early morning stiffness, preservation of function... 

To study the importance of KC-HC cell interaction in sepsis, we developed a rat KC and HC coculture model. An entire range of KC to HC ratios were tested (0.5 1 to 10 1). LPS was used as the relevant septic stimulus. As anticipated, the addition of even small amounts of LPS resulted in induction of acute phase reactant synthesis (Kispert et al., 1990). Of greater interest was a profound decrease in total protein synthesis seen when higher concentrations of LPS (0.1 /rg/ml or greater) was added to KC-HC cocultures with KC HC ratios greater than 2 1 (Figure 1). The decrease was first detected at 6-8 hr and became maximal at 24 hr. 

LPS can provoke a multi-organ failure, due to the secretion of acute-phase reactants such as platelet-activating factor (PAF), TNF-a, and LBP. Multi-organ failure is also due to the secretion of prostaglandin E2 (PGE2) and inflammatory cytokines such as TNF-a, IL-ip, IL-6, whose production may increase the secretion of the acute-phase reactant, LBP [63], thus constituting an amplifying loop. The presence of a tumor may modify this host response as will be discussed below. 

The innate system also provides for synthesis of small antibiotic peptides called defensins12 31-33 as well as larger proteins. Some of these proteins constitute the complement system, while others are described as acute-phase reactants. Some defensins are also cytokines, which attract lymphocytes. 

A rapid tic immunoaffinity chromatographic method has been reported for quantitation in serum of an acute phase reactant, C-reactive protein (CRP), which can differentiate between viral and bacterial infections. 

Ogawa, M., Pancreatic secretory trypsin inhibitor as an acute phase reactant. Clin. Biochem. 21, 19-25 (1988). 

Rahel BM, Visseren FL, Suttorp MJ, et al. Preprocedural serum levels of acute-phase reactants and prognosis after percutaneous coronary intervention. Cardiovasc Res 2003 60 136-140. 

Many mediators of inflammation have been identified— cytokines IL-6, tumor necrosis factor alpha cell adhesion molecules intracellular adhesion molecule-1 (ICAM-I), P-selectin and acute phase reactants CR.R fibrinogen, serum amyloid A, and soluble CD40 (Fig. I) (3). Myeloperoxidase is an enzyme secreted from monocytes, neutrophils, and macrophages. A single measurement taken from patient with chest pain in the emergency department predicted the early risk of myocardial infarction and the risk of major cardiac of ends in the next 30 days to six months (15). 

In experimental serum sickness, a fall in serum complement level occurs at the time immune complexes form and inflammatory lesions develop (D6). However, levels of complement do not always reflect activation or consumption by immune complexes. The rate of synthesis of complement proteins may be sufficient to replace the amount being consumed, and several of the complement components are so-called acute-phase reactants, i.e., their levels rise with inflammation. Thus, activation may occur despite normal or even elevated levels in the serum. Turnover studies provide more direct evidence of complement utilization but are technically cumbersome (K4). A simpler approach is the detection of split products of complement components, which provides direct evidence of complement activation, or the examination of effusions for evidence of complement depletion (H31, N7, P7). 

Tobias, P.S., Soldau, K., Ulevitch, R.J. Isolation of a lipopolysaccharide-binding acute phase reactant from rabbit serum. J Exp Med 164 (1986) 785-793. 

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