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)

We have investigated the involvement of interleukin-6 (IL-6) in the induction of the gene encoding the acute-phase protein human C-reactive protein (hCRP). In transgenic mice the hCRP gene can be induced by lipopolysaccharide (LPS), but not by IL-6. In contrast, hCRP was inducible by IL-6 in primary human hepatocytes and in primary hepatocytes isolated from transgenic mice. To further evaluate the role of IL-6, we introduced the hCRP transgene into animals lacking endogenous IL-6 (IL-6-negative mice). Here, hCRP was not inducible by LPS, but was induced by a combination of LPS and IL-6. These results clearly demonstrate that IL-6 is necessary, but not sufficient, for the induction of hCRP expression. These animal models will allow further dissection of the cytokine network responsible for the regulation of the major human acute-phase reactant CRP.
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PMID:Interleukin-6 is necessary, but not sufficient, for induction of the humanC-reactive protein gene in vivo. 927 Oct 80

Patients with sepsis or after major surgery have decreased plasma levels of the anticoagulant protein antithrombin. In such patients elevated levels of interleukin-6 (IL-6) are present and this interleukin is known to induce positive and negative acute phase responses. To investigate the possibility that antithrombin acts as a negative acute phase response-protein we performed studies on the human hepatoma cell line HepG2 in vitro and baboons in vivo. HepG2 cells were treated with recombinant human IL-6, IL-1beta, or combinations of the latter two, and tested for production of antithrombin, fibrinogen and prealbumin (transthyretin). This treatment resulted in a dose dependent increase in fibrinogen concentration (with a maximum effect of 2.8-2.9-fold) and a dose dependent decrease in prealbumin (with a maximum effect of 0.6-0.7-fold) and antithrombin concentrations (with a maximum effect of 0.6-0.8-fold). Simultaneous treatment of the HepG2 cells with IL-6 (1,000 pg/ml or 2,500 pg/ml) and IL-1beta (25 pg/ml), provided more extensively decreased prealbumin (0.8 and 0.6-fold, respectively) and antithrombin concentration (0.7 and 0.6-fold, respectively) compared to the single interleukin treatment at these concentrations. Baboons treated with 2 microg IL-6 x kg body-weight(-1) x day(-1) showed increased plasma CRP levels (59-fold, p <0.05) and decreased prealbumin (0.9-fold, p <0.05) and antithrombin (0.8-fold, p <0.05) plasma levels, without evidence for coagulation activation. Our results indicate that antithrombin acts as a negative acute phase protein, which may contribute to the decreased antithrombin plasma levels observed after major surgery or in sepsis.
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PMID:Antithrombin acts as a negative acute phase protein as established with studies on HepG2 cells and in baboons. 930 58

The aim of this study was to evaluate the feasibility, toxicity and efficacy of escalating doses of subcutaneous recombinant interleukin-6 (IL-6) in children with solid tumours in relapse. Recombinant IL-6 was administered subcutaneously once daily for 14 consecutive days, with a 14 day follow-up period. The starting dose for IL-6 was 1 microgram/kg/day and was escalated in subsequent patients groups until 10 micrograms/kg. Doses were escalated every 3 patients, provided that grade III or IV organ toxicity did not occur at the preceding dose level. Twelve patients were treated, three at each dose level. No grade 3-4 major organ toxicity was observed. Flu-like symptoms and fatigue were the most common side effects. All these symptoms resolved after the end of IL-6 administration. Significant increases in acute-phase proteins (CRP [C reactive protein], fibrinogen) and ESR (Erthrocyte sedimentation rate) were observed in all patients. Stimulatory effects on thrombocytopoiesis were observed at every dose level, and were maximal at 5 micrograms/kg and 10 microgram/kg. There was no tumour response observed during IL-6 administration. Pharmacokinetic profiles performed in 3 patients are consistent with previous reports in adults. IL-6 is a promising new cytokine for paediatric oncology, in particular to increase thrombocyte counts. We recommend that further studies in children proceed at a dose of 5-10 micrograms/kg/day in a once or, better, twice daily administration.
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PMID:Phase I study of interleukin-6 in children with solid tumours in relapse. 938 24

Efficacy and safety of panipenem/betamipron (PAPM/BP) in treatment of obstetric and gynecological infections, and change of interleukin-6 (IL-6) and interleukin-8 (IL-8) levels in blood, as markers of infection, were investigated. The results were as follows; 1) Clinical efficacy of PAPM/BP by drip infusion of 1-2 g/day for 3-14 days against 52 patients with intrauterine infection (n = 29), pelveoperitonitis (n = 19), and other infections were 14 "Excellent" in 14 cases, "Good" in 35 cases, and efficacy rate was 94.2% (49/52). Both efficacy rate analy by causative organisms and eradication rate were 35/37 (94.6%). No subjective or objective side effects and no abnormal labolatory findings were observed. 2) Changes of IL-6 (> 4 pg/ml) levels in serum, as an infection marker, were observed in 8 cases out of 14 cases (57.1%), and correlation between CRP and IL-6 in the treatment process was noticed. However, changes of serum IL-8 (> 12.5 pg/ml) were observed in only 2 cases of those 14 cases (14.3%), indicative that IL-8 has no significance as a marker of infection.
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PMID:[Change of cytokines and clinical efficacy of panipenem/betamipron in obstetric and gynecological infections. Yamagata Study Group of Panipenem/Betamipron in Obstetric and Gynecological Infections]. 955 75

The relationship between the proliferating cell nuclear antigen (PCNA) expression in renal cell carcinoma (RCC) determined by immunohistochemical staining using the PC10 clone, and the preoperative serum interleukin-6 (IL-6) value determined by ELISA was examined. The secretion of IL-6 in RCC was also examined immunohistochemically using an anti-IL-6 antibody. The PCNA labeling rate was significantly higher in grade 3 tumors than in grade 1 tumors (p < 0.05), but there were no significant differences between the other grades or TNM stages. No significant correlation was obtained between the serum level of IL-6 or the positive cell rate of IL-6 and the pathological grade of the RCC. A correlation was observed between the PCNA labeling rate and positive cell rate, and between the serum IL-6 value and CRP or ESR. In conclusion, the secretion of IL-6 was detected in RCC tissue, and was suggested to be a tumor factor responsible for the growth and spread of RCC. The serum IL-6 value is considered to reflect the total secretion of IL-6 produced by the RCC and accessory cells, i.e., monocyte-macrophage lineage cells, endothelial cells and fibroblasts.
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PMID:[The relationship between the production of interleukin-6 and the proliferating cell nuclear antigen (PCNA) expression in renal cell carcinoma]. 961 18

Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis has been suggested as a model for acute pancreatitis (AP), which allows evaluation of early alterations in the time course of the disease. The influence of the clinical course on procalcitonin (PCT), serum amyloid A (SAA), and several proinflammatory and inhibitory cytokines was evaluated in patients with AP following ERCP. Blood samples were prospectively collected from patients undergoing ERCP. The incidence of ERCP-induced pancreatic damage, defined as abdominal complaints, a threefold increase of serum lipase, and elevation of CRP from <10 to >20 mg/liter was 12.8% (12/94). Only mild clinical courses of acute pancreatitis were observed. PCT significantly increased in subjects with post-ERCP pancreatitis after 24 hr. However, PCT levels did not exceed 0.5 ng/ml in any patient. Interleukin-1 receptor antagonist (IL-1RA) began to differ from baseline 2 hr after ERCP, followed by interleukin-6 (IL-6, 6 hr), solubilized tumor necrosis factor-alpha receptor II (sTNF-alphaRII, 24 hr) and SAA (24 hr). Interleukin 10 (IL-10) showed marked interindividual variations with no obvious peak. Among all parameters evaluated, only peak values of IL-6 and IL-10 showed significant correlations with the reported pain score (r2 = 0.62/0.78), degree of ampullar irritation (r2 = NS/0.87), and the duration of ERCP (r2 = 0.58/0.76). No correlation was found with the volume of the injected contrast agent. We conclude that IL-10 and IL-6 appear to be useful to monitor patients after ERCP. The absence of any PCT elevation in the present study is in accordance with the clinical course of the patients who suffered from mild pancreatic damage without systemic or infectious complications.
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PMID:Diagnostic relevance of interleukin pattern, acute-phase proteins, and procalcitonin in early phase of post-ERCP pancreatitis. 972 66

We introduced thoracoscopic esophagectomy with extended lymphadenectomy for reduction of respiratory dysfunction and less surgical intervention in July 1995. In this study, we investigated the changes in serum interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1ra) levels in 8 patients (TS Group) who underwent thoracoscopic esophagectomy with extended lymphadenectomy and compared them with the changes in patients who underwent conventional thoracotomy (CT Group). The duration of the operation and intrathoracic procedure in the TS group were significantly longer than in the CT group. However, the amount of blood loss and intrathoracic blood loss of the TS group were not significantly higher than in the CT group. The number of dissected lymph nodes was not significantly larger. The serum IL-6 levels reached maximum levels 3 hours from the end of operation. In the TS group, the changes in IL-6 levels were significantly larger (p < 0.05). On the other hand, the changes in CRP levels were also significantly larger (p < 0.01). Significant correlation was observed between the duration of the intrathoracic procedure and the maximum levels of IL-6. On the other hand, serum IL-1ra levels were not significantly. At present, these results suggest that the surgical intervention of thoracoscopic esophagectomy are more larger than that of conventional thoracotomy. We think that the length of intrathoracic procedure of thoracoscopic esophagectomy may make more large surgical stress.
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PMID:[Changes of serum cytokine levels after thoracoscopic esophagectomy]. 1003 40

We investigated the serum concentration of interleukin-6 (IL-6) and four IL-6 family cytokines - oncostatin M (OSM), leukaemia inhibitory factor (LIF), interleukin-11 (IL-11) and ciliary neurotrophic factor (CNTF) as well as IL-6 soluble receptor (sIL-6R) - using an enzyme-linked immunosorbent assay (ELISA) in 67 patients with multiple myeloma (MM) and 24 healthy controls, for a possible association between the serum levels of these peptides with disease activity and known prognostic factors. sIL-6R was detectable in all 67 and IL-6 in 65 (97%) patients. Both peptides were measurable in all healthy controls. In contrast, OSM was detectable in 30 (44.8%) MM patients and in only four (16.6%) normal individuals. The serum levels of IL-6, OSM and sIL-6R were significantly higher in MM patients compared with control group (P < 0.001, P < 0.03 and P < 0. 001 respectively). The highest concentrations of these cytokines were found in patients with progressive disease and the lowest in MM patients with stable disease and in healthy persons. LIF was detectable in four (6%), CNTF in 28 (41.8%) and IL-11 in eight (11. 9%) of the patients with MM. In the control group LIF, CNTF and IL-11 were measurable in 8.3%, 33.3% and 8.3% respectively. The serum concentration of these cytokines did not correlate either with clinical stage or with the phase of disease and was similar to those in healthy individuals. We found significant positive correlation between IL-6 levels and OSM (P < 0.001). We also observed positive correlation between beta2-M concentration and serum levels of IL-6 (P < 0.002), sIL-6R (P < 0.02) and OSM (P < 0.04) as well as a positive relationship between CRP and IL-6 (P < 0.001) and OSM (P < 0.002). In conclusion, the serum levels of IL-6, OSM and sIL-6R, but not LIF, IL-11 and CNTF, may be useful markers of MM activity.
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PMID:Circulating IL-6-type cytokines and sIL-6R in patients with multiple myeloma. 1023 12

We experienced four cases with hyponatremia due to SIADH, which seems to be related to inflammation. The plasma Na concentration decreased when the patients had fever and increased plasma CRP level. In such conditions, plasma vasopressin concentration (PAVP) and the plasma interleukin-6 (IL-6) concentration were increased. There was significant correlation between them. The animal experiments were carried out to investigate the role of interleukin in the development of SIADH. Intravenous administrations of IL-1 beta increased AVP, atrial natriuretic hormone (ANH) and ACTH. The changes in AVP and ACTH were abolished by the pretreatment with an intravenous administration of indomatacin. Moreover, the intracerebroventricular administration (ICV) of IL-1 beta also increased AVP, atrial natriuretic hormone (ANH) and ACTH. The pretreatment of indomatacin attenuated the changes in AVP and ACTH. The intravenous administration of IL-1 beta increased the urinary sodium excretion. The pretreatement of HS142-1, an ANH antagonist, abolished the increase in urinary sodium excretion induced by IL-1 beta. These results suggested that the interleukin play an important role in the development of SIADH associated with inflammation.
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PMID:[Hyponatremia and inflammation]. 1037 61

Changes in immune function due to surgical injury have been well-documented. Immunosuppression is one of the causes of infectious complications leading to organ dysfunction in critical illness. It is not known what kind of surgery in the daily clinical practice causes immunosuppression. Stress response and immune function following surgery for esophageal carcinoma, assuming a highly-stressed operation, were studied and then compared with the stress response and immune function following gastric surgery, a moderately-stressed procedure. Forty patients who underwent esophagectomy and 39 patients receiving gastric operation were studied. The concentrations of serum interleukin-6 (IL-6) were measured preoperatively, at 1, 2, and 6 h, and at 1, 3, and 10 d after operation. Total protein, serum albumin, rapid turnover protein, serum CRP, and cortisol were measured before operation and at 1, 3, 7, and 21 d after operation. ConA- and PHA-stimulated lymphocyte proliferation, IgA, IgG, and IgM were also measured preoperatively, and on 7 and 21 d following surgery. The patients were fed exclusively by total parenteral nutrition (TPN). A striking rise of IL-6 was observed, with a peak in both groups at 1 to 6 h following operation. The peak values were 419+/-30 pg/mL, which was approximately twice as high in the esophagectomy patients as in the gastrectomy patients (195+/-40 pg/mL). CRP and cortisol also increased after operation, and these increases were also significantly greater in the esophagectomy patients. ConA- and PHA-stimulated lymphocyte proliferation decreased significantly 7 d after esophagectomy (P<0.05), but was unchanged in the patients receiving gastrectomy. Suppression of cellular immunity correlated significantly with serum cortisol, and was preceded by a rise in serum IL-6. The IgA, IgG, and IgM levels, however, remained unchanged from their preoperative values throughout the study in both groups. Nutritional status in terms of serum protein, albumin, and rapid turnover protein, decreased postoperatively, but there was no difference between the two groups. It is, therefore, concluded that cell-mediated immunosuppression, preceded by a hyperinflammatory response, is an observable reaction in patients following esophageal surgery, but not in patients undergoing gastric surgery.
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PMID:Changes in immune function following surgery for esophageal carcinoma. 1050 Dec 89


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