Acute-phase response

Family of transcription factors that modulate the expression of genes which control immune, inflammatory, and acute-phase responses, as well as cell growth, responses to stress, apoptosis, and oncogenesis. All members of this family have a Rel-homology domain that contains sequences responsible for dimerization and DNA binding. In vertebrates, this family includes NF-kB1 (also known as p50), NF-kB2 (also known as p52), Rel (also known as cRel), Rel-A (also known as p65), and Rel-B. 

Morimoto, A., Murakami, M., Takada, M., Teshirogti, S., Watanabe, T. (1987). Fever and the acute phase response induced in rabbits by human recombinant interferon. J. Physiol. 391, 209-218. 

Acute phase response proteins (eg, C-reactive protein, a,-acid glycoprotein [orosomucoid])... 

IL-6 T lymphocytes, monocytes, macrophages, synovial fibroblasts Activates T lymphocytes, induces acute-phase response, stimulates growth and differentiation of hematopoietic precursor cells stimulates synovial fibroblasts... 

IL-6 (21-28) Monocyte/macrophage, T cell endothelium, fibroblast, keratinocyte Induction of fever and the hepatic acute phase response. Stimulates cortisol production. Decreases IL-1 and TNF production. Participates in activation of B and T cells, facilitates Ig production by B cells. Induction of granulocyte-macrophage colony-stimulating factor, stimulation of hematopoietic progenitors. 

Most cytokines are pleiotropic, i.e. can affect a variety of cell types. Moreover, the effect that a cytokine has on one cell type may be the same or different to its effect on a different cell type. IL-1, for example, can induce fever, hypotension and an acute phase response. G-CSF is a growth factor for neutrophils, but it is also involved in stimulating migration of endothelial cells and growth of haematopoietic cells. IFN-y stimulates activation and growth of T- and B-lymphocytes, macrophages, NK cells, fibroblasts and endothelial cells. It also displays weak anti-proliferative activity with some cell types. 

IL-6 participates in both atherogenesis and inflammatory processes. In one interesting mouse model that was double deficient at the apoE and IL-6 loci, animals displayed similar hypercholesterolemia compared to apoE-null mice, but disclosed larger and more calcified lesions at 1 year of age (Klinge 2001). Thus, IL-6 appears to be involved at the fibrous plaque stage of the atherosclerotic process. Moreover, IL-6 is a key factor in the generation of the hepatic acute-phase response and so increases the levels of CRP, fibrinogen, platelet... 

These are generated by the liver during infections and other forms of inflammatory challenge, as part of the acute-phase response. This response to infection is characterised by fever, sleep, adrenotrophic hormone release, decreased plasma iron and zinc levels, elevated neutrophils in the bloodstream and enhanced cytokine production. These changes, part of the body s response to combat infection, occur within hours. The elevated temperatures may inhibit the replication of some bacteria and viruses and may also enhance the function of some immune cells. 

The acute-phase response is characterised by the enhanced (two- to threefold) synthesis of a number of proteins, such as antiproteinases, complement components, fibrinogen and ceruloplasmin, which are normally synthesised at fairly low rates. The rate of synthesis of some proteins is enhanced 100-1000-fold - for example, C-reactive protein, a-macroglobulin and acid-1-glycoprotein. Thus, serum levels of these proteins serve as indicators of disease. 

LI 1. Ledue, T. B., Neveux, L. M., Palomaki, G. E., Ritchie, R. F., and Craig, W. Y., The relationship between serum levels of lipoprotein(a) and proteins associated with the acute phase response. Clin. Chim. Acta 223, 73-82 (1993). 

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). 

The human hemopexin gene has been cloned (38) and is located near the P-globin gene cluster on human chromosome 11 (39). The promoters of the human, rat, and mouse hemopexin genes have been cloned, and the human gene contains a liver specific element (40) and an interleukin-6 responsive element (41), consistent with the positive acute phase response ofhemopexin (33,34). 

Cytokines, Interferons, and the Acute-Phase Response System... 

The body responds in many ways to infection, injury, or cancer. These include the secretion of cytokines, interferons, and proteins of the acute phase response. These proteins, many of which are quite... 

Dinarello CA. 1984. Interleukin-1 and the pathogenesis of acute phase response. NEJM. 311 1413-1418. 

Proinflammatory cytokines, released by activated macrophages and monocytes during infection, can act on neural targets that control thermogenesis, behavior, and mood. In addition to induction of fever, cytokines induce other biological functions associated with the acute-phase response, including hypophagia and sleep. Cytokine production has been detected within the central nervous... 

Cytokines are proteins involved in intercellular communication and are produced by many cell types. Cytokines are best known as mediators of the acute-phase response to microbial challenge and to tissue damage. For instance, cytokines are responsible for somnolence and sleep (as well as fever, anorexia, social withdrawal, and other symptoms of the acute-phase response) during infectious diseases. However, cytokines in much smaller concentrations may also have a role in physi-... 

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