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)

The potential for 41.8 degrees C whole body hyperthermia (WBH) to enhance ionizing irradiation and cytotoxic chemotherapy without a commensurate increase in normal tissue toxicity is currently receiving renewed clinical interest. Additionally, WBH may have other biological sequela which may be clinically exploited. In this paper, data are summarized revealing the ability of WBH to induce elevated plasma levels of granulocyte-colony stimulating factor (G-CSF), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNF-alpha) within hours of WBH. Data regarding TNF-alpha shows induction in only a proportion of patients. No induction of C-reactive protein (CRP) or the following cytokines was observed: granulocyte macrophage-colony stimulating factor (GM-CSF), interferon-gamma (IFN-gamma), interleukin-1 alpha (IL-1 alpha), interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-7 (IL-7), interleukin-11 (IL-11), interleukin-12 (IL-12), macrophage-colony stimulating factor (M-CSF), and macrophage inflammatory protein-1 alpha (MIP-1 alpha). Data regarding interleukin-3 (IL-3) and transforming growth factor-beta 1 (TGF-beta 1) were variable and inconclusive. The implications of these results to past and future clinical trials are discussed.
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PMID:Cytokine induction by 41.8 degrees C whole body hyperthermia. 749 63

Recent immunocytochemical data have demonstrated increases in interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and the IL-6-inducible acute phase protein, alpha 2-macroglobulin (alpha 2-M), in Alzheimer's disease (AD) brains. We investigated the levels of these proteins quantitatively using ELISA procedures and determined if increases in IL-1 beta were compensated for by a parallel increase in the endogenous interleukin-1 receptor antagonist (IL-1RA). Comparing control vs. Alzheimer's temporal cortex, we examined mature IL-1 beta, IL-1RA, IL-6, alpha 2-M and C-reactive protein (CRP). The specificities of the ELISA procedures were verified by serial dilutions of the samples; by chromatofocusing, and by Sephadex G-150 gel filtration. There were no differences in the levels of mature IL-1 beta or IL-1RA in AD and control brains. However, IL-6 levels were detectable in 14 of the 16 Alzheimer samples but only 2 of the 14 control samples. There were also significant increases seen in alpha 2-M and CRP levels in the Alzheimer's group compared to controls. These data support previous studies demonstrating a possible up-regulation of neuroimmune function in Alzheimer's cortex; however, we cannot determine, at this time, if this immune reaction is initiated by IL-1 beta.
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PMID:Cytokine indices in Alzheimer's temporal cortex: no changes in mature IL-1 beta or IL-1RA but increases in the associated acute phase proteins IL-6, alpha 2-macroglobulin and C-reactive protein. 750 48

Serum concentrations of the cytokine, interleukin-6 (IL-6), increase after surgical trauma. IL-6 mediates the synthesis of acute phase proteins and stimulates secretion of pituitary hormones. We have examined the time course of circulating IL-6, and cortisol and growth hormone responses in patients undergoing hysterectomy to determine if IL-6 contributes to the early pituitary hormone changes found during surgery. One group (n = 8) received a standardized general anaesthetic while the remaining patients (n = 8) received extradural analgesia to T4-S5 in addition to a similar general anaesthetic. In the general anaesthesia group, there was a significant increase in serum cortisol and growth hormone concentrations before any changes in IL-6 were detected. Furthermore, in the extradural group, in whom these hormonal responses were attenuated, circulating IL-6 concentrations did not differ significantly from the general anaesthesia group. There were no significant differences between the groups in the acute phase response, as measured by circulating concentrations of C-reactive protein and zinc, but the expected effects of extradural block on circulating metabolites and white cell count were demonstrated. We conclude that IL-6 is unlikely to contribute to the initial increases in secretion of pituitary hormones found during surgery, but a later effect of the cytokine on endocrine responses cannot be excluded.
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PMID:Effects of extradural anaesthesia on interleukin-6 and acute phase response to surgery. 751 May 10

Tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) play a main role in inducing acute phase protein production by hepatocytes. This study describes the serum levels of TNF alpha and IL-6 in relation to serum levels of C-reactive protein (CRP) and alpha 1-acid glycoprotein (alpha 1AG) in three systemic lupus erythematosus (SLE) patients. Disease courses of these patients were divided in a total of 19 clinical periods, according to the clinical symptoms and interleukin profiles. Significantly elevated TNF alpha levels were found in all but three of the defined periods, without being associated with disease activity. In only four of the defined periods elevated TNF alpha were observed combined with elevated IL-6 and CRP levels. Two of these periods coincided with minor symptoms of SLE, one with an exacerbation and the other one with a systemic infection while SLE activity was low. All other periods showed varying combinations of elevated TNF alpha and/or IL-6 levels being followed or not by elevated CRP levels. Significantly raised alpha 1AG levels were measured in all clinical periods. In most of the observed periods a dissociation was found between TNF alpha and IL-6 and also between the different cytokine (TNF alpha and IL-6) levels and acute phase protein (CRP and alpha 1AG) levels. These data could not be explained by differences in disease course or influences of medication. We conclude that more factors other than TNF alpha and IL-6 must play a role in the regulatory pathway of the acute phase response in SLE.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Profiles of cytokines (TNF alpha and IL-6) and acute phase proteins (CRP and alpha 1AG) related to the disease course in patients with systemic lupus erythematosus. 751 Oct 20

We investigated 37 patients with ascites and liver cirrhosis in order to examine whether on the basis of correlation of cytokines and acute phase proteins of the ascitic fluid, prognosis of spontaneous bacterial peritonitis can be made. Significantly enhanced levels of interleukin-6, as well as acute phase reactants alpha-1-antitrypsin and C-reactive protein were found in the ascitic fluid of patients with spontaneous bacterial peritonitis. The levels of tumour necrosis factor alpha (TNF-alpha), neopterin, interleukin 2-receptor and granulocyte-macrophage colony stimulating factor were higher in patients with spontaneous bacterial peritonitis, but without statistical significance, whereas no differences were found between the interferon gamma, interleukin-2 and interleukin-1 levels. In addition, interleukin-6, TNF-alpha and neopterin levels were found to correlate significantly with the outcome of the disease. These findings show that acute phase reaction occurs in the ascitic compartment in correlation with the development of spontaneous bacterial peritonitis.
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PMID:Spontaneous bacterial peritonitis is associated with high levels of interleukin-6 and its secondary mediators in ascitic fluid. 751 36

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

The in vitro effects of sera of 11 patients with liver cirrhosis on protein synthesis in PLC/PRF/5 cells were studied. Hepatitis B virus (HBV) infection was documented in 7 patients. Increased random production of several cell proteins of M(r) of approximately 25, 65, 90 and 130 K was shown by SDS-polyacrylamide gel electrophoresis (SDS-PAGE). There was no correlation between HBV-positive and HBV-negative cirrhosis and the induced proteins. One of them was identified as alpha-1 foetoprotein by immunoblot analysis. C-reactive protein (CRP) was determined only in one case; production of interleukin-6 (IL-6) was not detected.
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PMID:Effect of sera of cirrhotic patients with or without hepatitis B virus infection on protein synthesis in hepatoma cells. 752 Jun 65

High serum level of bioactive interleukin-6 (IL-6) is regarded as a predictor of poor prognosis in multiple myeloma (MM). On the other hand, the reported levels of immunoreactive IL-6 have been highly variable, and the prognostic value of immunoreactive IL-6 in MM is not clear. We have analyzed the prognostic significance of serum immunoreactive IL-6, as measured by a sensitive immunosorbent assay, in 210 patients with newly diagnosed MM subsequently treated with intermittent melphalan and prednisone. The serum levels of acute phase proteins C-reactive protein (CRP), alpha 1-antitrypsin (alpha 1AT), and acid alpha 1-glycoprotein (orosomucoid; OM) were evaluated as surrogates for IL-6. Serum IL-6, CRP, alpha 1AT, and OM levels were raised in 42%, 40%, 41%, and 24% of the patients, respectively. There was a significant correlation between the clinical stage of the patients and serum IL-6 (P = .006), alpha 1AT (P = .001), and OM (P = .004) levels at diagnosis. At 3 years, 52% of the patients were alive. Univariate logistic regression analysis showed that high levels of IL-6 (P = .002), CRP (P = .02), alpha 1AT (P < .001), OM (P = .007), beta 2-microglobulin (beta 2M; P < .001), and thymidine kinase (P < .05) were all associated with 3-year mortality. In multivariate regression analysis, beta 2M (P < .0001) and alpha 1AT (P = .01) had independent prognostic significance. The patients with high levels of both beta 2M and alpha 1AT or IL-6 were at very high risk of dying within 3 years from diagnosis (16% and 21% of the patients in these groups were alive, respectively). When the patients were stratified according to the clinical stage, the prognostic significance of serum IL-6 and alpha 1AT was especially evident in stage II patients. When the patients were divided into two groups according to normal or raised serum IL-6 levels, the patients with high IL-6 levels had more frequent osteolytic bone lesions (P = .03) and a more aggressive disease. We conclude that serum immunoreactive IL-6 is a significant prognostic marker in MM.
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PMID:Immunoreactive interleukin-6 and acute phase proteins as prognostic factors in multiple myeloma. Finnish Leukemia Group. 753 May 7

Cytokines, especially tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) play an important role in the genesis and progression of the septic shock syndrome. We performed a study monitoring levels of these three cytokines in ten neutropenic oncology patients in whom an infectious syndrome was suspected. A comparison was made with a population of nine non-neutropenic patients on the intensive care unit. Unfortunately the results of this study do not allow specific profiles to be established for each cytokine in the populations studied. Levels of IL-6, TNF alpha and IL-1 beta were not statistically higher in the non-neutropenic patients when compared with the neutropenic group. However, the highest IL-6 levels were observed for four non-neutropenic patients, three of whom died. High levels of C-reactive protein (CRP), haptoglobin and fibrinogen were found, reflecting the inflammatory status of each patient. CRP levels were higher in the non-neutropenic patients and correlated with IL-6 levels, indicating the importance of CRP determination in this group of patients.
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PMID:TNF alpha, IL-1 beta and IL-6 plasma levels in neutropenic patients after onset of fever and correlation with the C-reactive protein (CRP) kinetic values. 753 Nov 79


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