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 (hepatocyte stimulating factor) is a 26 kd cytokine that plays a major role in the acute phase response, especially the hepatic aspects of the acute phase response. Patients with alcoholic hepatitis manifest many aspects of the acute phase response. In this 6-month study we evaluated serial plasma interleukin-6 levels in 30 consecutive patients with moderate to severe alcoholic hepatitis. Mean admission plasma interleukin-6 activity was markedly increased (49.8 +/- 8.5 U/ml, normal less than 5 U/ml) in patients with alcoholic hepatitis, and levels decreased with clinical improvement to 15.6 +/- 6.1 U/ml at 6 months. Admission interleukin-6 activity correlated significantly (r = 0.82) with the severity of liver disease as assessed by the discriminant function of Maddrey. Also measured were selected assays postulated to be regulated by interleukin-6, including serum albumin (2.3 +/- 0.1 gm/dl), which was significantly depressed; alpha 1-acid glycoprotein (52 +/- 5 mg/dl), which was within normal limits; and IgA (827 +/- 70 mg/dl) and C-reactive protein (3.03 +/- 0.51 mg/dl), which were significantly elevated. Interleukin-6 activity fell over time in a pattern similar to that of bilirubin and C-reactive protein. We suggest that plasma interleukin-6 may not only regulate many aspects of the acute phase response but also may be a marker of inflammation and severity of disease in alcoholic hepatitis.
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PMID:Increased plasma interleukin-6 concentrations in alcoholic hepatitis. 158 11

We investigated the potential role of interleukin-6 as a mediator of the acute-phase reaction (APR) in patients with acute myocardial infarction. Of the six patients studied, five demonstrated increased plasma interleukin-6 levels. Interleukin-6 levels began to increase at 14 hours (mean; range = 8 to 20 hours) after the initial complaints and reached maximal levels of 28 to 250 U/mL (normal values less than 10 U/mL) after 36 hours (mean; range = 24 to 52 hours). No correlation was seen between the size of the interfaction as indicated by creatine kinase MB assays and the extent of the interleukin-6 increases (r = 0.44; p = 0.38). As an indicator of the APR, plasma C-reactive protein (CRP) levels were measured. CRP levels began to increase after 16 hours (mean; range = 8 to 24 hours) and reached maximum levels of 56 to 322 mg/L (normal values less than 3 mg/L) after 65 hours (mean; range = 48 to 92 hours). The increase of the interleukin-6 level preceded the increase of the CRP level in three patients and was simultaneous in two patients. Maximal interleukin-6 levels correlated significantly with maximal CRP levels (r = 0.96; p = 0.002). Thus these findings indicate that interleukin-6 is an important endogenous mediator for the APR in patients with acute myocardial infarction.
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PMID:Interleukin-6 release and the acute-phase reaction in patients with acute myocardial infarction: a pilot study. 158 14

Serum levels of interleukin-1 (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and C-reactive protein (CRP) were investigated in patients with chronic liver diseases (CLD) and correlated with the type of underlying disease and various clinical and laboratory parameters. Two hundred sixty-four patients suffering from various CLD were studied; 136 cases presented with liver cirrhosis, and 128 patients were in the noncirrhotic stage of their underlying liver diseases. Serum levels of IL-1 beta, IL-6, TNF-alpha, IFN-gamma, and CRP were elevated in patients with CLD. Endogenous cytokine patterns in CLD were stage dependent and only marginally affected by the type of underlying disease. The cirrhotic group of CLD patients showed higher serum levels in IL-1 beta, IL-6, TNF-alpha, and CRP than did noncirrhotic cases, and these differences reached the level of statistical significance. IL-1 beta and TNF-alpha values were closely correlated but did not correlate with IL-6 levels. Elevated concentrations of cytokines represent a characteristic feature of CLD regardless of underlying disease. This and the apparent stage-dependency suggest that enhanced endogenous cytokine levels represent a consequence of liver dysfunction rather than of inflammatory disease.
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PMID:Serum levels of cytokines in chronic liver diseases. 851 60

Human hepatocytes in primary culture were used as a model system to investigate the mechanism(s) involved in the induction of the acute-phase response in human liver. Hepatocytes were incubated with increasing amounts of recombinant human interleukin-1 beta, recombinant interleukin-6 and tumor necrosis factor-alpha. Synthesis of C-reactive protein was studied at the mRNA and protein levels. Only recombinant interleukin-6 was capable of inducing C-reactive protein-mRNA and C-reactive protein-protein synthesis. Also, fibrinogen and alpha-1-antitrypsin synthesis measured by immunoprecipitation with specific antisera increased in a dose-dependent, time-dependent manner, whereas albumin synthesis decreased to about 50% of controls. Maximal effects were observed at 100 to 300 units of recombinant interleukin-6/ml culture medium after 20 hr of incubation. Although the synthetic glucocorticoid dexamethasone slightly modulated the effect of recombinant interleukin-6, it was not an absolute requirement for the induction of acute-phase protein synthesis in human hepatocytes. In pulse-chase experiments it was shown that the time course of the disappearance of the acute-phase proteins from the cells and their appearance in the medium is not influenced by recombinant interleukin-6. This finding suggests that recombinant interleukin-6 exerts its regulatory effect on acute-phase protein synthesis at the pretranslational level.
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PMID:Acute-phase response of human hepatocytes: regulation of acute-phase protein synthesis by interleukin-6. 169 62

Four plasma proteins, referred to as positive acute phase proteins because of increases in concentration following inflammatory stimuli, are reviewed: C-reactive protein (CRP), serum amyloid A protein (SAA), alpha 1-acid glycoprotein (AAG), and fibrinogen. The CRP and SAA may increase in concentration as much as 1000-fold, the AAG and fibrinogen approximately twofold to fourfold. All are synthesized mainly in the liver, but each may be produced in a number of extrahepatic sites. The role of cytokines in induction of the acute phase proteins is discussed, particularly the multiple functional capabilities of interleukin-6 (IL-6). Other cytokines that regulate acute phase gene expression and protein synthesis include IL-1, tumor necrosis factor alpha, interferon gamma, as well as other stimulatory factors and cofactors. The physicochemical characteristics of each protein are reviewed together with the molecular biology. For each protein, the known biological effects are detailed. The following functions for CRP have been described: reaction with cell surface receptors resulting in opsonization, enhanced phagocytosis, and passive protection; activation of the classical complement pathway; scavenger for chromatin fragments; inhibition of growth and/or metastases of tumor cells; modulation of polymorphonuclear function; and a few additional diverse activities. The role of plasma SAA is described as a precursor of protein AA in secondary amyloidosis; other functions are speculative. AAG may play an immunoregulatory role as well as a role in binding a number of diverse drugs. In addition to clot formation, new data are described for binding of fibrinogen and fibrin to complement receptor type 3. Finally, the concentration of each protein is discussed in a wide variety of noninfectious and infectious disease states, particularly in connective tissue diseases. The quantification of the proteins during the course of various acute and chronic inflammatory disorders is useful in diagnosis, therapy, and in some cases, prognosis.
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PMID:Properties of four acute phase proteins: C-reactive protein, serum amyloid A protein, alpha 1-acid glycoprotein, and fibrinogen. 170 51

Under strict observation of the ethical guidelines of the 1975 Declaration of Helsinki Human Research Committee, primary hepatocyte cultures were prepared from second-trimester fetal liver specimens. We have shown for the first time that fetal hepatocytes have the capacity to produce an acute-phase response on treatment with inflammatory mediators. Addition of interleukin-6 to the cultures resulted in strong induction of C-reactive protein and alpha-1-antichymotrypsin expression, whereas albumin expression was repressed. In contrast to interleukin-6, transforming growth factor-beta did not induce C-reactive protein expression. However, as in adult hepatocytes, fetal cells responded to transforming growth factor-beta by reduced albumin synthesis. We were able to show by virtue of fluorescein excretion into sealed clefts that fetal hepatocytes have the functional capacity to form bile. Our findings indicate that second-trimester hepatocytes can be regarded as fairly mature liver cells.
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PMID:Human fetal hepatocytes respond to inflammatory mediators and excrete bile. 171 Oct 3

A patient with primary plasma cell leukemia resistant to chemotherapy was treated for 2 months with daily intravenous injections of anti-interleukin-6 (IL-6) monoclonal antibodies (MoAbs). The patient's clinical status improved throughout the treatment and no major side effects were observed. Serial monitoring showed blockage of the myeloma cell proliferation in the bone marrow (from 4.5% to 0% myeloma cells in the S-phase in vivo) as well as reduction in the serum calcium, serum monoclonal IgG, and the serum C-reactive protein levels. The serum calcium and serum monoclonal IgG corrected by approximately 30%, whereas the C-reactive protein corrected to undetectable levels during treatment. No major side effects developed, although both platelet and circulating neutrophil counts decreased during anti-IL-6 therapy. A transient immunization was detected 15 days after the initiation of the treatment, which could explain the recovery of myeloma cell proliferation after 2 months of treatment (2% myeloma cells in the S phase). In conclusion, this first anti-IL-6 clinical trial demonstrated the feasibility of injecting anti-IL-6 MoAbs, and also a transient tumor cytostasis and a reduction in IL-6-related toxicities. It gave insight into the major biologic activities of IL-6 in vivo and may serve as a basis for further development of anti-IL-6 therapy in myeloma and other IL-6-related diseases.
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PMID:Murine anti-interleukin-6 monoclonal antibody therapy for a patient with plasma cell leukemia. 171 18

This study sought to determine whether endogenous tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and granulocyte-colony-stimulating factor (G-CSF) were detectable in sera of lipopolysaccharide (LPS)-treated cancer patients. Twenty patients received an intravenous bolus of purified LPS from Salmonella abortus-equi (4.0 ng/kg). Patients were pretreated with ibuprofen (1,600 mg) to prevent constitutional side effects like fever and chills. Serum TNF-alpha levels increased from less than 0.01 ng/ml before treatment up to maximal levels of 21 ng/ml, peaking 1.5 h after LPS injection. Similarly, serum IL-6 concentrations increased from less than 0.01 to 11 ng/ml, but peak levels were obtained 30 min later than TNF-alpha. Circulating G-CSF appeared still later than TNF-alpha and IL-6. It was detectable within 3 h and peaked 6 h after LPS injection. Parallel to the release of the above cytokines a marked increase in granulocyte counts was observed. In all patients administration of LPS led to an acute-phase response as measured by C-reactive protein.
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PMID:Treatment of cancer patients with endotoxin induces release of endogenous cytokines. 171 15

Interleukin-6 has been shown to stimulate in vitro synthesis of C-reactive protein (CCRP) in hepatocytes by enhancing the transcriptional rate of the CRP gene. It has also been demonstrated that IL-6 spurs the terminal differentiation of B-cells into immunoglobulin secreting cells when synergizing with IL-3. IL-6 may therefore act as a prime molecule in the acute phase and immune response. We have administered rh IL-3 to cancer patients in a phase I/II clinical trial. Endogenous IL-6 levels increased in a dose-dependent fashion upon i.v. bolus injection of rh IL-3 and continued to be significantly elevated above pretreatment levels when IL-3 was further administered by the s.c. route. Increases of IL-6 levels were associated with enhanced production of CRP in vivo detected after 24 h of injection. At day 14 of rh IL-3 treatment plasma immunoglobulin concentrations were measured and IgM was found to be increased by greater than 2.5 fold above starting levels. These results indicate that rh IL-3 also augments the acute phase response in vivo and contributes to increased synthesis of IgM and that induction of endogenous IL-6 is involved in these events.
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PMID:In vivo administration of recombinant human interleukin-3 elicits an acute phase response involving endogenous synthesis of interleukin-6. 171 92

Postoperative serum interleukin-6 (SIL-6) and C-reactive protein (SCRP) levels were examined in 71 patients who underwent various types of abdominal surgery. Similar time-dependent changes in SIL-6 and SCRP levels were observed in 12 patients despite differences in surgical procedures and liver function among the patients. SIL-6 started to increase within 3 hours after the beginning of the operation and reached a peak after 24 hours. SCRP started to increase after 12 hours and was maximum at 48 to 72 hours. The increase in SIL-6 at 24 hours (delta IL-6) showed a close correlation with that of SCRP at 48 hours (delta CRP) in 53 patients without liver cirrhosis. In 18 patients with liver cirrhosis, delta CRP relative to delta IL-6 was less than that in patients without cirrhosis and was poorly correlated with the latter. delta IL-6 was correlated with the length of time of the operation and blood loss in both groups, but delta CRP showed no significant correlation with these factors in either group. These findings indicate that the increase in IL-6 triggered by a surgical procedure may function as a hepatocyte-stimulating factor and that monitoring of SIL-6 may be more helpful than monitoring of SCRP for estimation of inflammatory status and early detection of an acute-phase response.
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PMID:Interleukin-6 as a new indicator of inflammatory status: detection of serum levels of interleukin-6 and C-reactive protein after surgery. 173 91


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