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)

An improved knowledge of the initial prognostic factors of multiple myeloma and regular monitoring of the disease should result in the choice of the most effective treatment. The conventional prognostic factors have been divided into three stages by Durie and Salmon. These stages are based on the proportion and type of the monoclonal component, on haemoglobin, calcium and creatinine blood levels and on the extent of bone lesions. However, this widely used classification has certain disadvantages: the size of the tumoral mass is evaluated mainly from the proportion of monoclonal gammopathy, the bone lesions are difficult to determine and the kinetics of cell proliferation are not taken into account. Parameters with high prognostic value have recently been demonstrated; they include beta 2-microglobulin, LDH, interleukin-6, C-reactive protein, serum albumin and kinetic of cell proliferation. When associated, these data allow to establish prognostic staying that are at least as relevant as those of the Durie-Salmon's classification. Monitoring of patients with multiple myeloma by means of a time-related curve of either the tumoral mass or the amount of monoclonal gammopathy leads to the best possible treatment.
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PMID:[Prognostic factors and monitoring of myeloma]. 128 67

We used a BALB/c model of passive cutaneous anaphylaxis (PCA), an IgE-mediated, mast cell-dependent reaction, to demonstrate the early production of the proinflammatory cytokine interleukin-6 (IL-6) mRNA and protein product. Northern blot analysis detects IL-6 mRNA 1, and 2 hours after antigen challenge (dinitrophenyl30-40 human serum albumin [DNP30-40-HSA]) and in situ hybridization reveals that it is primarily cells with round-to-oval nuclei within the dermis (1 to 3 per high-power field) expressing IL-6 mRNA. Immunohistochemistry revealed perinuclear and cytoplasmic staining for immunoreactive IL-6 in mononuclear dermal cells and also cells within the basal keratinocyte layer. Injection of recombinant murine IL-6 (rmIL-6) either systemically or locally during antidinitrophenyl IgE skin sensitization resulted in increased vasopermeability at the PCA site after DNP30-40-HSA. However, this increased permeability was not associated with a change in the character of the cellular infiltrate at the PCA site 8 hours later. Although the specific role of IL-6 in the generation of the allergic response remains unknown, its detection during PCA unequivocally demonstrates that IL-6 be considered one of the mediators identified in inflammation that follows allergic reactions.
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PMID:Passive cutaneous anaphylaxis in mouse skin is associated with local accumulation of interleukin-6 mRNA and immunoreactive interleukin-6 protein. 143 Jul 7

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

The response of megakaryocytes and platelets to the administration of recombinant human interleukin-6 (IL-6) was investigated in normal and sublethally irradiated dogs. IL-6 was administered for 2 weeks at doses of 10 to 160 micrograms/kg/d to normal animals to assess dose-response and toxicity. Subsequently, 40, 80, or 160 micrograms/kg/d for 2 weeks was administered to animals treated with 200 cG total body irradiation. Analysis of normal dogs showed a significant increment in the platelet count detectable approximately 11 days after initiation of IL-6 at all administered doses. Large platelets greater than 6.3 microns in diameter were observed 1 day after beginning IL-6, progressively increasing to as many as 19.1% of the total circulating platelets by day 10. The ploidy distribution of the marrow megakaryocytes did not differ from the normal at doses of less than or equal to 80 micrograms/kg/d, but at 160 micrograms/kg/d, a shift toward higher ploidy cells was noted. No change in total white count was noted; however, a decrease in hematocrit was seen at all doses. In the irradiated animals, the platelet count recovered earlier in the IL-6-treated dogs than in the controls, but no consistent change in the ploidy distribution was observed irrespective of dose. Large platelets were also noted in the treated animals, comprising up to 6.9% of the total platelet count. Fibrinogen levels were elevated to greater than 4 times normal. A significant decrease in hematocrit was seen in all animals, while no consistent change was noted in the white count. Elevations in serum cholesterol, triglycerides, and alkaline phosphatase, together with a decline in serum albumin were observed in all the treated animals (both normal and irradiated), but clinical symptoms were observed only in the dogs receiving greater than or equal to 80 micrograms/kg/d. The data show that IL-6 alone is capable of enhancing platelet recovery in dogs with bone marrow suppression.
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PMID:Thrombocytopoiesis in normal and sublethally irradiated dogs: response to human interleukin-6. 162

A novel in-vitro system has been developed for the detection and quantification of pyrogen in pharmaceutical products. The measured variable was evoked secretion of the pyrogenic cytokine interleukin-6 from MONO MAC 6 monocytic cells incubated with the product. The interleukin-6 was detected using a specific and sensitive ELISA developed for this purpose. The test system detected pyrogenic contamination in 3 batches of therapeutic human serum albumin which had caused adverse reactions in recipients. The contamination was not detected in conventional tests: the rabbit pyrogen test and the limulus amoebocyte lysate test.
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PMID:Assay of pyrogens by interleukin-6 release from monocytic cell lines. 168 Oct 74

Peripheral venous plasma concentrations of interleukin-6 were studied in 21 patients with active Crohn's disease, 20 patients with ulcerative colitis, and 16 control subjects. Interleukin-6 was detected in the plasma of 18 of 21 patients with Crohn's disease (median 47 (range less than 20-250) pg/ml) but in only two with ulcerative colitis and two control subjects. In the patients with Crohn's disease there was a significant negative correlation between the plasma interleukin-6 and the serum albumin concentrations. In eight patients with Crohn's disease and five patients with ulcerative colitis undergoing resection plasma from peripheral circulation and mesenteric vein draining diseased intestine was studied. Interleukin-6 was detected in seven of eight peripheral and mesenteric samples from the patients with Crohn's disease but was not detected in any of the samples from the patients with ulcerative colitis. There was no significant difference between mesenteric and peripheral samples in the concentrations of interleukin-6.
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PMID:High circulating concentrations of interleukin-6 in active Crohn's disease but not ulcerative colitis. 177 61

A thrombocytopoiesis-stimulating factor (TSF or thrombopoietin) derived from human embryonic kidney (HEK) cells is known to increase platelet production and to increase the number of morphologically unrecognizable early megakaryocytes, ie, small acetylcholinesterase-positive (SAChE+) cells in mice. Other recent studies have concluded that interleukin-6 (IL-6) also stimulates murine megakaryocytopoiesis both in vitro and in vivo. Some workers have suggested that IL-6 is thrombopoietin. Therefore, the purpose of this study was to compare the effects of TSF and IL-6 on percent 35S incorporation into platelets, platelet sizes, and the percentages of SAChE+ cells in C3H mice, and to determine if they produce the same or different responses. The results showed that two or four injections of a partially purified TSF (total dose of 2 or 4 units (U) over a 1- or 2-day period) increased percent 35S incorporation into platelets (P less than .005) and platelet sizes (P less than .005) of both normal and rebound-thrombocytotic mice when compared with values from other mice treated with human serum albumin, the carrier protein for both TSF and IL-6. In eight separate experiments, it was shown that IL-6 (40,000 U, 4 micrograms), when given to rebound-thrombocytotic mice in four injections over a 2-day period, produced a small but significant (P less than .005) increase in percent 35S incorporation into platelets. Additional studies showed that negative results were obtained when similar high doses of IL-6 were administered in two doses over a 1-day period. TSF, but not IL-6, stimulated an increase in platelet sizes of normal mice (P less than .005 to 0.0005); however, IL-6 increased platelet sizes of rebound-thrombocytotic mice when given in two of four injections (P less than .05 to .0005). Also, IL-6, but not TSF, caused anemia in normal mice (P less than .0005) that were given two injections and tested 3 days later. TSF stimulated an increase (P less than .005) in the percentage of SA-ChE+ cells; whereas IL-6, even at high doses, did not. Because of the observed differences in biologic responses of these two cytokines, we conclude that TSF and IL-6 are separate entities.
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PMID:Comparative effects of thrombopoietin and interleukin-6 on murine megakaryocytopoiesis and platelet production. 199 16

In cynomolgus monkeys, twice daily subcutaneous injections of recombinant human interleukin-6 (rhIL-6) at doses of 5 to 80 micrograms/kg/d for 14 consecutive days caused dose-dependent increases in platelet count, usually continuing for more than 1 week after cessation of the injections. The count reached a level approximately twofold or more above the preinjection level even at 5 micrograms/kg/d, and at doses of more than 20 micrograms/kg/d, the increase became biphasic with a higher second peak 3 days after cessation of the injections. Morphologic analysis of the bone marrow after the 7 day-injections with 80 micrograms/kg/d revealed a marked increment in size of megakaryocytes compared with control, indicating the promotion of megakaryocyte maturation. Other changes attributable to the rhIL-6 treatment include dose-dependent loss of body weight, anemia, neutrophilia and monocytosis, elevation of serum C-reactive protein and alpha-1 acid glycoprotein levels, and decrease of serum albumin; all of which returned to normal within 1 week after cessation of the injections and were tolerable at doses of less than 10 micrograms/kg/d. These findings suggest that rhIL-6 may be an effective strategy for the treatment of thrombocytopenia.
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PMID:In vivo effects of recombinant human interleukin-6 in primates: stimulated production of platelets. 232 12

Paired serum and cerebrospinal fluid (CSF) specimens from 14 patients with systemic lupus erythematosus (SLE) and central nervous system (CNS) involvement were studied for interleukin-6 (IL-6) activity using the IL-6-dependent murine hybridoma, MH60.BSF2. We also studied 23 patients with noninflammatory neurologic diseases, and 9 SLE patients without CNS involvement. CSF IL-6 activity was elevated only in SLE patients with CNS involvement, although there was no significant difference in serum IL-6 activity among the 3 groups. CSF IL-6 activity was not correlated with either the CSF-serum albumin quotient (Q albumin; an indicator of blood-brain barrier function) or serum IL-6 activity in SLE patients with CNS involvement. The CSF IL-6 activity decreased significantly when CNS manifestations subsided after successful treatment. These results indicate that determination of CSF IL-6 activity may be useful in the evaluation of CNS disease activity in SLE. Moreover, the data confirm the presence of immune system activation within the CNS in patients with SLE-associated CNS disease.
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PMID:Elevated levels of interleukin-6 in cerebrospinal fluid from patients with systemic lupus erythematosus and central nervous system involvement. 234 20

We established an interleukin-6 (IL-6)-dependent cell line from murine plasmacytoma MOPC-104E cells. This cell line (designated PIL-6) was found to respond to murine and to human IL-6, but not to any other cytokines. We used this cell line to investigate the involvement of IL-6 production in type II collagen-induced arthritis in DBA/1 mice. Only marginal IL-6 activity was detected in sera from DBA/1 mice inoculated with Freund's complete adjuvant (FCA) alone, with an unrelated protein (bovine serum albumin) plus FCA, or with type II collagen plus Freund's incomplete adjuvant. However, enhanced IL-6 activity was observed in DBA/1 mice that had been injected with type II collagen plus FCA to induce arthritis. The elevated level of serum IL-6 activity was associated with high levels of IL-6 produced when lymph node cells from arthritic mice were stimulated in vitro with type II collagen. We also found that the L3T4+ T cell subset is responsible for the enhanced production of IL-6 in arthritic mice. The results are discussed in the context of potential roles of IL-6 in the induction and/or expression of chronic, progressive arthritis.
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PMID:Enhanced production of interleukin-6 in mice with type II collagen-induced arthritis. 278 99


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