Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-6 (IL-6) has been ascribed significant roles in both hematopoiesis and the immune response, although its contribution to host defence as a whole is poorly understood. Because short-term IL-6 treatment was previously shown to stimulate megakaryocytopoiesis, we investigated the effect of long-term administration of IL-6 on megakaryocytopoiesis and other systemic parameters in nonhuman primates. We chose a small primate, the marmoset (Callithrix jacchus), which enabled long-term administration at high doses. Recombinant human IL-6 (rhIL-6) administered at doses of up to 1,000 micrograms/kg/d over 4 and 9 weeks caused a sustained twofold to threefold increase of thrombocyte counts, peaking at 4 weeks. Thrombocyte counts declined thereafter, despite continuing IL-6 administration. The number of bone marrow megakaryocytes at 4 and 9 weeks was not increased compared with controls, but the ploidy grade was augmented, suggesting that IL-6 effects are restricted to mature megakaryocytes in vivo. An acute-phase protein response was observed within 24 hours after the first IL-6 administration and reached a maximum after 1 week of IL-6 administration at 25 micrograms/kg. Serum C-reactive protein, haptoglobin, and ceruloplasmin were increased, whereas albumin and transferrin levels declined. The acute-phase protein response was not associated with any morphologic evidence of hepatocellular damage. The increased levels of Ig and soluble IL-2 receptor in the serum levels reflected systemic immunostimulation. There was no evidence of renal mesangioproliferative pathology. Antibodies against rhIL-6 developed within 2 weeks, continuously increasing during the course of the study. High titers of neutralizing antibodies appeared concomitantly with the decrease in platelet counts and decline in acute-phase proteins. Therefore, despite the pleiotropic effects of IL-6 observed in vitro, long-term administration of IL-6 caused a selective and sustained stimulation of thrombopoiesis in marmosets that was only ablated by the appearance of neutralizing antibodies, and high doses were well tolerated in marmosets. A long-term targeting of IL-6 to cells of the megakaryocytic lineage, without evoking general toxicity, confirms the potential therapeutic usefulness of rhIL-6 for the chronic treatment of thrombocytopenic patients.
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PMID:Long-term interleukin-6 administration stimulates sustained thrombopoiesis and acute-phase protein synthesis in a small primate--the marmoset. 751 39

The relationship among "negative" plasma acute-phase proteins (APP), ie, albumin, prealbumin, and transferrin, and "positive" APP, ie, C-reactive protein (CRP), fibrinogen, and orosomucoid, was investigated in patients with acute infectious disease (n = 8) and in patients with chronic malignant disease (n = 9). In addition, the transcapillary escape rate (TER) and outflux (J(alb)) of albumin were investigated using an intravenous injection of 2 microCi 125I-albumin. Interleukin-6 (IL-6) plasma concentrations were measured with an enzyme immunoassay. In the majority of patients, negative APP were decreased, whereas positive APP were increased. However, in patients with infectious disease, there were no significant correlations between any of the negative and positive APP. Also, in patients with infectious disease, TER was increased to 8.6 +/- 3.4%/h (mean +/- SD), and J(alb) to 114 +/- 60 mg/kg/h, compared with normal values of 4.3 +/- 2.6%/h and 108 +/- 7 mg/kg/h, respectively. Unexpectedly, there was a significant positive correlation between plasma albumin and both TER (r = .8279, P = .011) and J(alb) (r = .8683, P = .005). In patients with malignomas, significant correlations within negative and positive APP and inverse correlations between negative and positive APP resulted. Malignant disease induced only a slight elevation in TER (6.6 +/- 2.4%/h), J(alb) was within normal limits (92 +/- 35 mg/kg/h), and no correlations between plasma albumin concentrations and TER (r = -.0174, P = .97) or J(alb) (r = .4090, P = .27) were found.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transcapillary escape rate of albumin positively correlates with plasma albumin concentration in acute but not in chronic inflammatory disease. 751 58

In the present study, interleukin-6 (IL-6) and several acute phase proteins were measured in healthy participants (23-87 years of age). A linear correlation between IL-6 and age was established with an increase of 0.016 pg/ml (0.004) per year of life. Whereas CRP remained below 0.5 mg/dl in all participants, an increase with age for fibrinogen and an inverse relation for albumin as well as transferrin were obtained. However, the increase of IL-6 did not correlate with any of these changes. IL-6 associated diseases may therefore occur more often with advancing age, but in healthy participants IL-6 does not explain the changing plasma protein pattern resembling that of an acute phase reaction.
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PMID:Interleukin-6 and selected plasma proteins in healthy persons of different ages. 753 83

Serum levels of alpha 1-antichymotrypsin (alpha 1-ACT) were measured in patients with early and late onset Alzheimer's disease (e-AD, 1-AD), patients with vascular dementia (VD) and healthy elderly. Patients with 1-AD were divided into two groups, one had normal alpha 1-ACT values and one had increased serum levels of alpha 1-ACT. Other acute phase proteins were also measured. The serum levels of alpha 2-macroglobulin (alpha 2-MG), alpha 1-antitrypsin (alpha 1-AT), ceruloplasmin (CER), transferrin (TRSF) and alpha 1-acid glycoprotein (alpha 1-ac.GL) were within the normal range. The C reactive protein (CRP) was occasionally detectable at low concentrations in e-AD, in both groups of 1-AD patients and in VD patients. Low serum concentrations of interleukin-6 (IL-6) were found in a higher proportion of 1-AD than in patients with e-AD or VD. These results indicated that increased levels of alpha 1-ACT along with occasional detection of IL-6 might be peripheral markers of the 'acute reaction' in the brain.
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PMID:Increased serum alpha 1-antichymotrypsin in patients with probable Alzheimer's disease: an acute phase reactant without the peripheral acute phase response. 753 91

Initial studies have shown that recombinant human interleukin-6 (rhIL-6) induces anemia. Until now, the pathophysiologic mechanism of this induced anemia has been unknown. To unravel the underlying mechanism, we examined 15 cancer patients receiving rhIL-6 as an antitumor immunotherapy in a phase II study. rhIL-6 was administered subcutaneously at 150 micrograms once daily for 6 consecutive weeks. Various hematologic and biochemical parameters were measured weekly during rhIL-6 treatment and 4 weeks after rhIL-6 discontinuation. To determine plasma volume and red blood cell (RBC) volume, radioisotope dilution assays with labeled autologous RBCs and with human serum albumin were performed before rhIL-6 administration and on day 8 of rhIL-6 therapy. Hemoglobin levels decreased (mean change +/- SE) 7% +/- 1.5% within 3 days after the start of rhIL-6 therapy (P < .0001) and 19% +/- 2% at week 4. Levels had normalized at follow-up. The plasma volume increased 18% +/- 5% during the first week of rhIL-6 administration (P < .003), whereas RBC volume remained unaffected. The mean RBC corpuscular volume remained unchanged for 2 weeks and then began to decrease slowly, reaching its nadir at week 6 (5% +/- 1%; P < .01). Serum iron levels decreased 65% +/- 12% at week 4 (P < .002) and then returned to initial baseline values. Erythropoietin levels increased rapidly up to 68% at week 3 (P < .0001) and had normalized 4 weeks after rhIL-6 therapy. Levels of serum albumin, prealbumin, and transferrin decreased (P < .0001, P < .003, and P < .0001, respectively), whereas levels of serum amyloid A (P < .003), C-reactive protein, haptoglobin, and alpha-1-antitrypsin (P < .0001) increased during rhIL-6 treatment. All levels returned to pretreatment values after discontinuation of rhIL-6. No alterations in reticulocyte counts, serum lactic dehydrogenase levels, and bilirubin levels were observed. A 6-week regimen of subcutaneous rhIL-6 results in a rapid dilution anemia, caused by an acute and significant increase in plasma volume and followed by hypoferremia. This anemia is reversible after the cessation of rhIL-6 treatment.
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PMID:Recombinant human interleukin-6 induces a rapid and reversible anemia in cancer patients. 754 2

The decrease in haemoglobin concentration commonly observed after major surgery is usually corrected by red cell transfusions or oral iron medication. The increased awareness of blood-transmissible diseases has led to the restrictive use of homologous blood and to interest in alternatives for correcting anaemia. We investigated the pathophysiology of postoperative anaemia by studying variables of erythropoiesis, iron metabolism, and inflammation in 48 consecutive patients who underwent total hip replacement. Haemoglobin concentration remained low during 14 days after surgery with only a mild increase in erythropoietin concentration and reticulocyte count. No increase in serum transferrin receptor concentration was observed during the first 2 weeks after surgery. Postoperative serum ferritin increased, whereas serum iron, transferrin and transferrin saturation decreased significantly. There was a marked increase in interleukin-6 and C-reactive protein with maximal values on the 1st and 4th post-operative day, respectively. At 6 weeks after surgery, haemoglobin concentration and variables of iron metabolism were almost at the preoperative level and serum transferrin receptor concentration was significantly increased, indicating increased erythropoietic activity. These changes were preceded by the normalization of interleukin-6 and C-reactive protein levels. Haemoglobin, iron, transferrin, and ferritin concentrations were not influenced by iron therapy during the postoperative period and no differences of erythropoietic and iron variables were observed between transfused and non-transfused patients. In conclusion, post-operative erythropoiesis is associated with an inflammatory effect of surgery on iron metabolism, which can explain, despite a slightly increased production of erythropoietin, the persistence of anaemia and the lack of effect of iron supplementation after surgery.
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PMID:Post-operative erythropoiesis is limited by the inflammatory effect of surgery on iron metabolism. 765 15

There is some evidence that schizophrenia may be accompanied by alterations in cell-mediated immunity (CMI) and that antipsychotic agents may modulate CMI. The purpose of this study was to investigate the plasma levels of interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), sIL-2R, and transferrin-receptor (TfR) in schizophrenia and mania, and the effects of treatment with neuroleptics or mood stabilizers on these variables. The subjects were 14 schizophrenic patients, 10 manic patients and 21 healthy volunteers. The above immune variables were measured in baseline conditions and after treatment with neuroleptics in schizophrenic patients and valproate in manic patients. Plasma concentrations of IL-6, sIL-6R, sIL-2R and TfR were significantly higher in the combined group of psychotic patients than in healthy volunteers. Plasma IL-6 was significantly higher in schizophrenic patients, while plasma sIL-6R and sIL-2R were significantly higher in mania than in normal controls. In schizophrenic patients, plasma levels of IL-6, sIL-6R and TfR were significantly lower after treatment with neuroleptics than before treatment. No significant effects of valproate on the immune-inflammatory markers could be found in the manic patients. It is suggested that activation of CMI may occur in both schizophrenia and mania and that neuroleptics may have immunosuppressive effects through suppression of IL-6 or IL-6R-related mechanisms.
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PMID:Interleukin-2 and interleukin-6 in schizophrenia and mania: effects of neuroleptics and mood stabilizers. 766 81

HepG2 cells were cultured for 7 days in serum-free medium in the presence of interleukin-6 (IL-6), retinoic acid (RA) or dexamethasone (DX), and some plasma proteins secreted to the media were determined by electroimmunoassay whereas the contents of specific mRNAs in the cells was evaluated by Northern blot hybridization. Interleukin-6 maximally stimulated synthesis of alpha-1-antichymotrypsin between days 1 and 3 whereas the response of fibrinogen was delayed to days 3 to 7. Retinoic acid increased the effect of IL-6 on alpha-1-antichymotrypsin (ACT) and fibrinogen (FBG) on the level of both proteins and mRNAs. Synthesis of albumin was slightly inhibited by IL-6 and RA, and synthesis of transferrin was increased by RA but not by IL-6. Dexamethasone had small enhancing effect on the action of IL-6. These results suggest that long-term HepG2 cultures may provide an experimental model for liver acute phase response during chronic inflammation.
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PMID:Long-term culture of HepG2 hepatoma cells as a model for liver acute phase response during chronic inflammation. Effects of interleukin-6, dexamethasone and retinoic acid. 769 40

Suppression of proliferation of cells which contain stable or stabilized mRNA coded for a protein to be produced, a partial mimic of cell differentiation, was examined for enhancing protein production by cultured mammalian cells. Hybridoma 2E3 cells which were adapted to be interleukin-6 sensitivity growth-suppressed accumulated the mRNA of IgG1 which is reported stable, and IgG1 production rate increased as a result when their growth was suppressed with interleukin-6. A myeloma cell line was similarly adapted; the obtained myeloma cells can be used as host cells for enhancing production of exogenous proteins by suppressing growth with interleukin-6. Temperature-sensitively growth-suppressible mutants of mouse mammary carcinoma FM3A were transfected with cDNA of IgM lambda 1 chain and cultured at nonpermissive temperature to enhance production of lambda 1. Addition of various growth-suppressive reagents to culture medium was studied for finding methods suitable for suppressing growth while maintaining high cell viability. Caffeine yielded the best results among these reagents. Deprivation of various growth-supporting components in culture medium was also tested; simultaneous deprivation of insulin and transferrin viably suppressed growth of hybridoma 2E3 cells, resulting in enhanced antibody productivity.
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PMID:Growth rate suppression of cultured mammalian cells enhances protein productivity. 776 53

Despite much research, the pathophysiology underlying lower L-tryptophan (L-TRP) availability in major depression has remained elusive. The present study investigates whether lower L-TRP availability in major depression is related to immune activation which may occur in that illness and is known to modulate L-TRP metabolism. Toward this end, the authors have measured the following in depressed patients and normal control subjects: plasma levels of L-TRP, and the competing amino acids (CAA) valine, leucine, isoleucine, tyrosine, and phenylalanine, together with indices of immune function such as haptoglobin (Hp) and transferrin (Tf) plasma levels, dipeptidyl peptidase IV (DPP IV) serum activity, and mitogen-induced culture supernatant interleukin-6 (Il-6) production. Both plasma levels of L-TRP and the L-TRP/CAA ratio were significantly lower in major depressed subjects as compared with healthy control subjects. There were significant correlations between plasma L-TRP levels, on the one hand, and Tf plasma levels, DPP IV activity (both positive), Il-6 production, and Hp plasma levels (both negative), on the other. Up to 63.7% of the variance in L-TRP plasma concentrations could be explained by DPP IV, Hp, Il-6 values, and gender. Up to 50% of the variance in the L-TRP/CAA ratio could be explained by Hp values (negative correlation) and gender. It is hypothesized that lower plasma L-TRP availability in major depression may be related to the immune response in that illness.
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PMID:Relationships between lower plasma L-tryptophan levels and immune-inflammatory variables in depression. 790 45


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