Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.16.3.1 (ceruloplasmin)
 5,074 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is now generally recognized that interleukin-6 (IL6) is one of the cytokines that mediate the various nonspecific host defense responses to infectious pathogens. Among its now well-demonstrated effects on systemic administration are fever and acute-phase proteinemia. These effects are also activated by the cytokine, IL1, and it has been shown that they are modulated in the preoptic-anterior hypothalamus (POA). This study was undertaken to determine whether this brain region similarly drives the febrile and proteinemic responses to IL6. We compared, therefore, these responses of conscious guinea pigs to human recombinant (hr)IL6 administered intravenously (IV) and into the POA. hrIL6 given IV was not pyrogenic at 1 microgram/kg, caused low-grade, dose-independent fevers (0.4 +/- 0.1 degree C) at 5-20 micrograms/kg, and dose-related fevers at 50 and 100 micrograms/kg (0.6 +/- 0.0 and 0.9 +/- 0.1 degree C, respectively). However, all doses of hrIL6 induced elevations in the plasma levels of ceruloplasmin (as an indicator of acute-phase proteins), albeit not in a dose-dependent manner. Indomethacin (10 mg/kg, injected intramuscularly 20 min before hrIL6) abolished the febrile response, but did not prevent the rise in plasma ceruloplasmin levels. Fever and ceruloplasminemia were also evoked by 50 and 100 ng of hrIL6 injected into the POA (1 microliter bilaterally), but not by 25 ng. These results indicate that the inductions of fever and plasma ceruloplasmin by IL6 are, like those of IL1, modulated in the POA, albeit the effective doses are much higher than those of IL1.
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PMID:Neuromodulation of acute-phase responses to interleukin-6 in guinea pigs. 212 80

Interleukin 6 (IL6) is the new definition of a group of cytokines previously named according to their biological activity, e.g. B cell stimulatory factor 2 (BSF-2), hybridoma plasmocytoma-growth factor (HGF), interferon-beta 2 (IFN-beta 2), hepatocyte stimulating factor (HSF). It has recently been suggested that IL6 may represent the major mediator of acute-phase protein response whereas IL1 beta and TNF-alpha could play a minor role. We compared the effect of the three cytokines on hepatic protein synthesis by performing in vitro as well as in vivo experiments. Human hepatoma cells (PLC/PRF5) were exposed to each cytokine separately for 20 h, and the effect was then studied at the protein and RNA level. All three cytokines reduced albumin and increased C3 and ceruloplasmin biosynthesis. The cytokines induced the same effect at the RNA level indicating that the modulation was pretranslational. The effect of the cytokines was specific since actin gene expression was not changed; furthermore the effect was blocked by specific antibodies against the cytokines. The effect of the single cytokines was dose and time dependent, and quantitatively comparable. None of the cytokines was able to alter alpha 1-anti-trypsin synthesis. In vivo experiments with mice showed that IL1 beta and TNF-alpha both induce serum amyloid A (SAA) mRNA in the mouse liver and increase factor B (Bf) gene expression. Human recombinant IL6 induced SAA gene expression and it also had a weak positive effect on Bf gene expression after i.p. injection. These data demonstrate that the three cytokines studied are quantitatively and qualitatively comparable, and that all three are probably involved in acute-phase protein response.
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PMID:Interleukin 6, the third mediator of acute-phase reaction, modulates hepatic protein synthesis in human and mouse. Comparison with interleukin 1 beta and tumor necrosis factor-alpha. 313 37

The acute phase proteins (APPs) have been empirically defined as those whose plasma concentration changes following inflammatory reaction. Those proteins whose concentrations increase are referred to as positive APP, while those whose levels decline are termed negative APP. In man, positive APP are: alpha 1 acid glycoprotein, alpha 1 protease inhibitor, alpha 1 antichymotrypsin, haptoglobin, ceruloplasmin, fibrinogen, C-reactive protein, serum amyloid A. Great variability in the APP response between different species is observed. The principal functions of APP, result from the interaction of these proteins with ligands of various origins which give "protein-ligands" complexes. These complexes are cleared by the RES or by the hepatocyte. The results are protease inhibition, neutralization of toxic molecules such as hemoglobin or the superoxide anion, clearance of cell membranes and chromatin. The drop of the plasma concentration of negative APP during an inflammatory reaction carries a rise of free ligands (fatty acids, hormones, vitamins, trace elements). IL6 has been recognized as the principal regulator of most APP genes. The response of the hepatic cell to IL6 is characterized by the enhanced production of type 2 or IL6 specific APPs. The biochemical process of signal transduction is IL6--JAK2--APRF The set of APP genes regulated by IL1 type cytokines (type 1 APPs) is distinct from that regulated by IL6 type cytokine. IL1 and TNF alpha mediated stimulation of type 1 APP genes is synergistically enhanced by IL6 type cytokines. The biochemical process of signal transduction is IL1, IL6--Ras--MAP kinase--NFIL6 The targeted inflammatory proteic profile including the assay of C-reactive protein, haptoglobin and alpha 1 acid glycoprotein produces a "biological tool" to the clinician in order to manage an inflammatory response. IL6, a proteic marker for the future, connected with CRP, will be assayed during early inflammatory reaction.
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PMID:[Acute-phase proteins in inflammation]. 856 70

The aim of this study was to investigate whether or not the human immune system can be activated by a noninfectious stimulus, thereby improving the physiological status of the individual. The effect of a single cold water immersion (14 degrees C for 1 h) on the immune system of athletic young men, monitored immediately after immersion, was minimal. With the continuation of the cold water immersions (three times a week for a duration of 6 weeks) a small, but significant, increase in the proportions of monocytes, lymphocytes with expressed IL2 receptors (CD25) and in plasma tumour necrosis factor alpha content was induced. An increase in the plasma concentrations of some acute phase proteins, such as haptoglobin and haemopexin, was also observed. After 6 weeks of repeated immersions a trend towards an increase in the plasma concentrations of IL6 and the amount of total T lymphocytes (CD3), T helper cells (CD4), T suppressor cells (CD8), activated T and B lymphocytes (HLA-DR) and a decrease in the plasma concentration of alpha 1-antitrypsin was observed. Concentrations of IL1 beta, neopterin, C-reactive protein, orosomucoid, ceruloplasmin, macroglobulin, immunoglobulins (IgG, IgM, IgA) and C3, C4 components of the complement, as well as the total number of erythrocytes, leucocytes, granulocytes and neutrophils showed no significant changes after the repeated cold water immersions. It was concluded that the stress-inducing noninfectious stimuli, such as repeated cold water immersions, which increased metabolic rate due to shivering the elevated blood concentrations of catecholamines, activated the immune system to a slight extent. The biological significance of the changes observed remains to be elucidated.
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PMID:Immune system of cold-exposed and cold-adapted humans. 892 15

Serum zinc and copper levels and serum interleukin 1 beta (IL1 beta) and tumour necrosis factor alpha (TNF alpha) levels were evaluated in 57 female patients with active rheumatoid arthritis (RA) to investigate a possible role of IL1 beta and TNF alpha on zinc and copper homeostasis in RA. Serum zinc levels were significantly lower and serum copper levels significantly higher in RA patients when compared with osteoarthritis or asymmetrical psoriatic oligoarthritis patients and with normal controls. No differences were observed in serum IgM rheumatoid factor positive and serum IgM rheumatoid factor negative patients as regards serum zinc and copper concentration. In RA patients the erythrocyte sedimentation rate and acute-phase proteins correlated negatively with serum zinc and positively with serum copper. IL1 beta and TNF alpha were found to correlate negatively with zinc and positively with copper in RA patients. Lower levels of zinc may be due to an accumulation of zinc-containing proteins in the liver and in the inflamed joints in RA. Elevated serum copper levels seem to be linked to the increased synthesis of ceruloplasmin by the liver.
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PMID:Serum zinc and copper in active rheumatoid arthritis: correlation with interleukin 1 beta and tumour necrosis factor alpha. 980 81

A localized acute phase response occurs in the brain in Alzheimer's disease. Acute phase proteins have previously been measured in brain homogenates to quantify this response. The extent to which measurements of these proteins reflect brain parenchymal contents, as opposed to vascular contents, is unknown. In this study, the acute phase proteins ceruloplasmin (CP), complement factor 3 (C3), haptoglobin (HP), and albumin were measured in regional brain homogenates from phosphate buffered saline-perfused and sham-perfused rats (n = 7-9/group). Interleukin 1-beta (IL1-beta) and copper were also measured. Mean CP, C3, HP, and albumin concentrations in perfused specimens decreased by 94%, 88%, 90%, and 81% vs. sham-perfused specimens (all p < 0.001), while IL1-beta and copper were unchanged. These results suggest that acute phase protein measurements in brain homogenates reflect primarily vascular contents. However, IL1-beta and copper concentrations in brain homogenates are minimally influenced by vascular contents.
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PMID:Measurement of acute phase proteins in the rat brain: contribution of vascular contents. 1049 28