Role of acute-phase proteins in interleukin-1-induced nonspecific resistance to bacterial infections in mice.

The mechanism(s) of stress-induced hypoferremia and hypozincemia remains unclear. We studied the role of granulocytes and lactoferrin (LF) in endotoxin and murine interleukin 1 (IL-1)-induced depression of serum Fe and Zn concentrations in both rabbits and rats. Both endotoxin and IL-1 administration induced significant hypoferremia (P less than 0.01) and hypozincemia (P less than 0.01) after 6 h in both species. Granulocyte depletion before IL-1 infusion significantly (P less than 0.01) diminished the hypoferremia but not the hypozincemia. Moreover, infusion of 5 or 15 mg of human LF into rabbits caused significant hypoferremia (P less than 0.005) without hypozincemia. Significant hypozincemia (P less than 0.01) could only be demonstrated after a 75-mg infusion. In contrast, infusions of human transferrin at equivalent doses (5, 15, and 75 mg) induced neither hypoferremia nor hypozincemia. Therefore endotoxin and IL-1-induced hypoferremia and, to a much lesser degree, hypozincemia are granulocyte dependent. Granulocyte released LF is a specific carrier molecule for transport and removal of Fe from the circulation during the acute phase response. The data suggest a mechanistic dissociation of IL-1-induced hypoferremia and hypozincemia with LF-independent mechanisms for Zn.

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Role of prostaglandins in acute phase proteins in inflammation

Biochemical Medicine ◽

10.1016/0006-2944(84)90028-0 ◽

1984 ◽

Vol 31 (2) ◽

pp. 236-245 ◽

Cited By ~ 14

Author(s):

K. Anbalagan ◽

J. Sadique

Keyword(s):

Acute Phase ◽

Acute Phase Proteins

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Adipokines: inflammation and the pleiotropic role of white adipose tissue

British Journal Of Nutrition ◽

10.1079/bjn20041213 ◽

2004 ◽

Vol 92 (3) ◽

pp. 347-355 ◽

Cited By ~ 1305

Author(s):

Paul Trayhurn ◽

I. Stuart Wood

Keyword(s):

Adipose Tissue ◽

Growth Factor ◽

Inflammatory Cytokines ◽

Acute Phase ◽

White Adipose Tissue ◽

Acute Phase Proteins ◽

Endocrine Function ◽

Low Grade ◽

Circulating Levels

White adipose tissue is now recognised to be a multifunctional organ; in addition to the central role of lipid storage, it has a major endocrine function secreting several hormones, notably leptin and adiponectin, and a diverse range of other protein factors. These various protein signals have been given the collective name ‘adipocytokines’ or ‘adipokines’. However, since most are neither ‘cytokines’ nor ‘cytokine-like’, it is recommended that the term ‘adipokine’ be universally adopted to describe a protein that is secreted from (and synthesised by) adipocytes. It is suggested that the term is restricted to proteins secreted from adipocytes, excluding signals released only by the other cell types (such as macrophages) in adipose tissue. Theadipokinome(which together with lipid moieties released, such as fatty acids and prostaglandins, constitute thesecretomeof fat cells) includes proteins involved in lipid metabolism, insulin sensitivity, the alternative complement system, vascular haemostasis, blood pressure regulation and angiogenesis, as well as the regulation of energy balance. In addition, there is a growing list of adipokines involved in inflammation (TNFα, IL-1β, IL-6, IL-8, IL-10, transforming growth factor-β, nerve growth factor) and the acute-phase response (plasminogen activator inhibitor-1, haptoglobin, serum amyloid A). Production of these proteins by adipose tissue is increased in obesity, and raised circulating levels of several acute-phase proteins and inflammatory cytokines has led to the view that the obese are characterised by a state of chronic low-grade inflammation, and that this links causally to insulin resistance and the metabolic syndrome. It is, however, unclear as to the extent to which adipose tissue contributes quantitatively to the elevated circulating levels of these factors in obesity and whether there is a generalised or local state of inflammation. The parsimonious view is that the increased production of inflammatory cytokines and acute-phase proteins by adipose tissue in obesity relates primarily to localised events within the expanding fat depots. It is suggested that these events reflect hypoxia in parts of the growing adipose tissue mass in advance of angiogenesis, and involve the key controller of the cellular response to hypoxia, the transcription factor hypoxia inducible factor-1.

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Mechanisms and implications of hypoalbuminemia in head-injured patients

Journal of Neurosurgery ◽

10.3171/jns.1988.69.3.0386 ◽

1988 ◽

Vol 69 (3) ◽

pp. 386-392 ◽

Cited By ~ 45

Author(s):

Craig J. McClain ◽

Bernhard Hennig ◽

Linda G. Ott ◽

Simeon Goldblum ◽

A. Byron Young

Keyword(s):

Endothelial Cell ◽

Acute Phase ◽

Nutritional Support ◽

Cell Injury ◽

Acute Phase Proteins ◽

Interleukin 1 ◽

Endothelial Permeability ◽

Content Type ◽

Head Injured ◽

Injured Patients

✓ Severely head-injured patients are hypermetabolic/hypercatabolic and exhibit many aspects of the postinjury acute-phase response. These patients have hypoalbuminemia, hypozincemia, hypoferremia, hypercupria, fever, and increased synthesis of acute-phase proteins such as ceruloplasmin and higher C-reactive protein levels. It has been suggested that increased interleukin-1 (IL-1) in the ventricular fluid may be responsible, at least in part, for these metabolic abnormalities. In the present study, serum albumin levels were evaluated throughout an 18-day study period in 62 head-injured patients receiving aggressive nutritional support. Hypoalbuminemia (mean ± standard error of the mean 3.10 ± 0.2 gm/dl; normal value 3.5 to 5 gm/dl) was observed upon hospital admission; these albumin levels continued to decrease until 2 weeks postinjury, despite aggressive nutritional support. This hypoalbuminemia may be mediated via altered endothelial permeability properties due to endothelial cell dysfunction caused by cytokines such as IL-1. Transendothelial movement of albumin was assayed using a pulmonary artery endothelial cell culture system. Both a crude macrophage supernatant derived from a murine P388D cell line having IL-1 activity (mIL-1) and human recombinant IL-1 (rIL-1) were tested. The amount of albumin transferred was time- and concentration-dependent, with maximal transfer at 24 hours and 20 U of mIL-1 per 0.5 ml of culture medium. Endothelial permeability changes observed after incubation with mIL-1 were confirmed using rIL-1. Compared to control cultures, 20 U of rIL-1 and 20 U of mIL-1 increased albumin transfer across endothelial monolayers 205% and 459%, respectively. These findings suggest that the mechanism of hypoalbuminemia seen after severe head trauma can be explained in part by IL-1-induced endothelial cell injury, resulting in enhanced endothelial permeability to albumin.

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Serum levels of proteins and acute-phase proteins in captive emus ( Dromaius novaehllandieae ) of different ages

Arquivo Brasileiro de Medicina Veterinária e Zootecnia ◽

10.1590/1678-4162-8926 ◽

2017 ◽

Vol 69 (2) ◽

pp. 405-408

Author(s):

P.A. Di Filippo ◽

I.S. Viana ◽

A.J. Almeida ◽

F.A.S. Graça ◽

A.B.F. Rodrigues ◽

...

Keyword(s):

Acute Phase ◽

Simple Technique ◽

Acute Phase Proteins ◽

Protein Profile ◽

Serum Levels ◽

Protein Electrophoresis ◽

Sds Page ◽

Dromaius Novaehollandiae ◽

Diagnosis Of Diseases

ABSTRACT Protein electrophoresis is a relatively simple technique that allows separating serum protein fractions, and provides important information in the investigation and diagnosis of several diseases. This study determined the levels of acute-phase proteins in the serum of healthy, captive emus (Dromaius novaehollandiae). Animals were divided into two groups (n=11 in each) based on age, with 1-year-old and 4-year-old emus. Acute-phase proteins were separated by SDS-PAGE. Ceruloplasmin, transferrin, albumin, haptoglobin, acidic glycoprotein, IgA, and IgG were detected in the serum of all animals. Protein profiles varied significantly with age (P<0.05). Individuals in the 4-year-old emus group had higher values of ceruloplasmin, transferrin, albumin, haptoglobin, and acidic glycoprotein, compared with the group with 1-year-old animals, showing the role of age in the protein profile of this species. Reference values for acute-phase proteins in healthy emus may be useful in the evaluation of health status and in the diagnosis of diseases affecting the species.

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Okadaic acid, an inhibitor of protein phosphatases 1 and 2A, inhibits induction of acute-phase proteins by interleukin-6 alone or in combination with interleukin-1 in human hepatoma cell lines

Biochemical Journal ◽

10.1042/bj2840645 ◽

1992 ◽

Vol 284 (3) ◽

pp. 645-648 ◽

Cited By ~ 11

Author(s):

M K Ganapathi

Keyword(s):

Acute Phase ◽

Okadaic Acid ◽

Interleukin 6 ◽

Acute Phase Proteins ◽

Protein Phosphatases ◽

Hepatoma Cell ◽

Interleukin 1 ◽

Dependent Manner ◽

Amyloid A ◽

20 Nm

Okadaic acid (OA), a specific inhibitor of protein phosphatases 1 and 2A, inhibited in a dose-dependent manner (5-20 nM) the induction of C-reactive protein (CRP), serum amyloid A (SAA) and fibrinogen by interleukin-6 (IL-6) plus interleukin-1 (IL-1), and of fibrinogen by IL-6 alone, in Hep 3B cells. Induction of alpha 1-proteinase inhibitor (alpha 1-PI) by IL-6 plus IL-1 or IL-6 alone was not significantly affected by OA up to concentrations of 20 nM, above which concentration OA was toxic in Hep 3B cells. OA also inhibited the induction of CRP, fibrinogen and alpha 1-PI by IL-6 in the NPLC/PRF/5 cell line, albeit at a higher concentration (80 nM). These results suggest that the signal transduction mechanisms regulating induction of acute-phase proteins by IL-6, either alone or in combination with IL-1, are mediated by activation of protein phosphatases 1 and/or 2A.

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