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 effects of SM-8849 on the development of autoimmune disease in MRL/Mp-1pr/1pr mice were examined. SM-8849 improved survival as well as renal disease, restored the deficits in splenic cell responsiveness to stimulation by mitogens or conventional antigens, and prevented lymphadenopathy and splenomegaly coincident with a decrease in the number of Thy-1+/Lyt-2-/L3T4- cells. SM-8849 also suppressed the production of the B-cell differentiation factor, possibly with a resulting preferential reduction of autoantibodies. In addition, SM-8849 depressed the production of hydrogen peroxide from macrophages. These results suggest that the administration of SM-8849 to a subject with autoimmune diseases can induce immunological improvements with possible clinical effectiveness.
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PMID:Alteration in progression of murine autoimmune disease by treatment with a novel immunomodulator, SM-8849. 178 57

The interleukin hypothesis relates chronic pathology in long-term end-stage renal disease (ESRD) patients to repeated stimulation of mononuclear cell cytokine production during hemodialysis. In vitro experiments demonstrated different possible mechanisms involved in hemodialysis-associated cytokine induction: adherence of mononuclear cells to the dialyzer membrane; complement activation, and the passage of cytokine-inducing bacterial fragments from contaminated dialysate through the dialyzer membrane into the blood. Studies investigating mononuclear cells from ESRD patients ex vivo suggest that these cells become activated during hemodialysis with complement-activating membranes and that the type of dialyzer membrane may influence mononuclear cell cytokine production in response to endotoxin. According to biological assays, plasma levels of interleukin-1 but not interleukin-6 activity seem to be elevated in ESRD patients compared to normal subjects and may increase further during treatment depending on the choice of the dialyzer membrane. However, to date, partly due to insufficient assay sensitivity and circulating inhibitors, measurements of interleukin-1, interleukin-6 and tumor necrosis factor in plasma by specific immunoassays could not finally prove elevated plasma cytokine levels in ESRD patients. Since circulating mononuclear cells are a major source of cytokines, studying the activation of these cells ex vivo seems to be the best approach to study hemodialysis-associated cytokine induction.
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PMID:Hemodialysis-associated induction of cytokines. 208 29

Aleutian mink disease (AD) is a naturally occurring persistent virus infection of mink caused by the Aleutian mink disease parvovirus (ADV). The classical form of AD, which occurs in adult mink, is notable for high titers of antiviral antibodies, hypergammaglobulinemia, plasmacytosis, and immune complex disease. In addition, there is a progressive renal disease characterized by mesangial proliferative glomerulonephritis and severe interstitial nephritis. Development of AD depends on both host and viral factors, and mink of certain genotypes fail to develop progressive disease when inoculated with low-virulence strains of virus. In newborn mink kits, ADV causes a fatal, acute interstitial pneumonitis associated with permissive viral replication in alveolar type 2 cells, but treatment of newborn kits with anti-viral antibody aborts the acute disease and converts into one resembling the persistent infection observed in adults. In infected adult mink, ADV is sequestered as immune complexes in lymphoid organs, but actual viral replication is restricted at the level of the individual cell and can be detected in only a small population of macrophages and follicular dendritic cells. ADV infection of mink primary macrophages and the human macrophage cell line U937 is antibody dependent and leads to the production of the cytokine interleukin-6. Furthermore, levels of interleukin-6 are increased in lymph node culture supernatants from infected mink. Chronic production of interleukin-6 may promote development of the immune disorder characteristic of AD.
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PMID:Aleutian mink disease: puzzles and paradigms. 788 16

Patients with end-stage renal disease present with an immunodeficient state paradoxically coexisting with signs of activation of immune system cells and that is accentuated rather than corrected by replacement dialysis therapy. The mechanisms of this immune system dysregulation presently under consideration are a reduced bioavailability of interleukin-2 secondary to its overconsumption by activated T cells; a downregulation of phagocyte adhesion molecules and opsonin receptors following their overexpression during dialysis with complement-activating membranes; an increased production of the cytokines interleukin-1, tumor necrosis factor-alpha, and interleukin-6 by activated monocytes and of soluble CD23 by B lymphocytes; and last, but far from least, the presence of uremic toxins. Perspectives of research are aimed at elucidating the respective role of the T helper cell subpopulations (Th-1 and Th-2) and the influence of the progression of chronic renal failure on the naturally occurring cytokine inhibitors, with the hope of better defining the rationale of strategies of immunomodulation that could be beneficial to patients with end-stage renal disease.
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PMID:The immune system in end-stage renal disease. 792 28

Human immunodeficiency virus infection is associated with the development of focal segmental glomerulosclerosis (FSGS). The majority of these patients with renal disease, however, are also cocaine abusers, but it is unknown what role cocaine may play in the development of focal segmental glomerulosclerosis. We undertook the present study to determine in vitro whether cocaine can modulate mesangial cell (MC) proliferation, a process believed to be a precursor to the development of glomerulosclerosis, either directly or indirectly via interaction with macrophages (M phi). Cocaine alone was not found to alter significantly either MC number or MC [3H]thymidine incorporation. However, when MC were incubated with secretory products collected from M phi preincubated with standard medium or medium containing cocaine, MC proliferation was found to be significantly enhanced with secretory products from M phi preincubated with cocaine in both serum-free (P < .001) and serum-stimulated conditions (P < .001). The effect of cocaine was found to be concentration-related. Pretreatment of macrophage secretory products from cocaine-treated M phi with neutralizing antibodies to transforming growth factor-beta significantly augmented the mitogenic effect of cocaine macrophage secretory products, and neutralizing antibodies to interleukin-6 significantly attenuated this effect. Direct incubation of MC with transforming growth factor-beta and interleukin-6 caused significant suppression and augmentation of MC proliferation, respectively. These data suggest that cocaine can modulate MC proliferation via interaction with M phi and that interleukin-6 and transforming growth factor-beta participate in this modulating effect. These results support a potential role for cocaine in the development of focal segmental glomerulosclerosis in patients with human immunodeficiency virus infection.
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PMID:Cocaine interacts with macrophages to modulate mesangial cell proliferation. 796 30

IgM mesangial nephropathy (IgMN) is a common pathologic finding in Taiwanese children with nephrotic syndrome. The hallmarks of IgMN are mesangial hypercellularity and IgM immune complex deposition in the mesangial area. In order to investigate whether the interleukin-6 (IL-6) and interleukin-1 (IL-1) protein production and gene mRNA expression are augmented in the local renal tissue of IgMN, we performed histobiochemical and mRNA studies using an immunopathologic technique and in situ hybridization. We also studied the correlation between urinary IL-6 levels and intensity of IL-6 expression in renal tissue. The results show that 15 cases of IgMN had overexpression with the highest score of both IL-6 and IL-1 proteins and mRNA expression in glomerular mesangial cells and diffuse distribution throughout the glomerular mesangium and capillary, Bowman's capsule, interstitium and renal tubule. In contrast, the patients with minimal change nephrotic syndrome and normal controls failed to show IL-6 and IL-1 mRNA overexpression. The urinary IL-6 levels of the patients with IgMN were highly correlated with the intensity of IL-6 protein expression in renal tissue. The higher the IL-6 overexpression, the higher was the rate of steroid resistance with focal sclerosis. These findings suggest that IL-6 and IL-1 mRNA amplification may play important roles in the pathogenesis of IgMN. The urinary level and degree of overexpression of IL-6 may serve as a prognostic parameter.
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PMID:Augmented expression of interleukin-6 and interleukin-1 genes in the mesangium of IgM mesangial nephropathy. 799 Oct 18

Interstitial cystitis is a syndrome of urinary urgency, frequency and suprapubic pain. We investigated the role of inflammatory mediators in 96 patients with histories and symptoms consistent with interstitial cystitis, and 13 controls from The New York Hospital-Cornell Medical Center, University of Washington and University of California at San Diego. Patients were classified into either group A (meets all criteria of the National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases for inclusion in research studies), group B (meets all of these criteria but without glomerulations) or an "other" group. A small number of group A patients had detectable interleukin-6 in the urine. Urinary concentrations of tumor necrosis factor, prostaglandins E2, D2 and F2 alpha, and thromboxane B2 were not different among either patient groups or controls. Urine specimens contained inhibitors of the bioactivity of interleukin-6 and tumor necrosis factors but no differences between patients or controls were found. No factors chemotactic for human neutrophils were detected in a small patient sample. Bladder wash fluid concentrations of prostaglandins E2, D2 and F2 alpha, and thromboxane were much lower than urinary levels. Bladder wash fluid interleukin-6 and tumor necrosis factor were not detectable. The results suggest that while a small subset of patients may have elevated levels of interleukin-6 the majority of patients do not appear to have elevated levels of inflammatory mediators in the urine or bladder wash fluid. Evaluation of patient bladder tissue may indicate changes not detectable in urine or bladder wash fluid. Alternatively, other etiologies must be considered in those patients.
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PMID:Inflammatory mediator profile in urine and bladder wash fluid of patients with interstitial cystitis. 801 71

The influence of blood-membrane interaction on human peripheral blood monocyte tumor necrosis factor-alpha (TNF), interleukin-6 (IL-6), and interleukin-8 (IL-8) secretion was measured during hemodialysis of end-stage renal disease patients by in vitro stimulation of whole blood with lipopolysaccharide. Monocyte TNF and IL-6 secretion in vitro was reduced 30 min after start of dialysis session. In contrast, cellular IL-8 secretion did not change during hemodialysis. Comparison of the results of three different membranes indicates that the bioincompatibility of the dialysis membrane was reflected in both leukocytopenia and reduction of cellular TNF secretion. During treatment of normal whole blood in an ex vivo dialysis closed-loop circuit, the ability of monocytes to release TNF, IL-6, and IL-8 in vitro remained constant. This indicates that the reduced IL-6 and TNF secretion during standard hemodialysis was not due to a direct effect of contact between dialysis membranes and monocytes, but rather was a result of redistribution within the patients' leukocyte pool.
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PMID:Effect of hemodialysis on peripheral blood monocyte tumor necrosis factor-alpha, interleukin-6, and interleukin-8 secretion in vitro. 801 41

The introduction of molecular therapy through the delivery of nucleic acids either as oligonucleotides or genetic constructs holds enormous promise for the treatment of renal disease. Significant barriers remain, however, before successful organ-specific molecular therapy can be applied to the kidney. These include the development of methods to target the kidney selectively, the definition of vectors that transduce renal tissue, the identification of appropriate molecular targets, the development of constructs that are regulated and expressed for long periods of time, the demonstration of efficacy in vivo, and the demonstration of safety in humans. As the genetic and pathophysiologic basis of renal disease is clarified, obvious targets for therapy will be defined, for example, polycystin in polycystic kidney disease, human immunodeficiency virus (HIV) type 1 in HIV-associated nephropathy, alpha-galactosidase A in Fabry's disease, insulin in diabetic nephropathy, and the "minor" collagen IV chains in Alport's syndrome. In addition, several potential mediators of progressive renal disease may be amenable to molecular therapeutic strategies, such as interleukin-6, basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), and transforming growth factor-beta(TGF-beta). To test the in vivo efficacy of molecular therapy, appropriate animal models for these disease states must be developed, an area that has received too little attention. For the successful delivery of genetic constructs to the kidney, both viral and nonviral vector systems will be required. The kidney has a major advantage over other solid organs since it is accessible by many routes, including intrarenal artery infusion, retrograde delivery through the uroexcretory pathways, and ex vivo during transplantation. To further restrict expression to the kidney, tropic vectors and tissue-specific promoters also must be developed. For the purpose of inhibition of endogenous or exogenous genes, current therapeutic modalities include the delivery of antisense oligodeoxynucleotides or ribozymes. For these approaches to succeed, we must gain a much better understanding of the nature of their transport into the kidney, requirements for specificity, and in vivo mechanisms of action. The danger of a rush to clinical application is that superficial approaches to these issues will likely fail and enthusiasm will be lost for an area that should be one of the most exciting developments in therapeutics in the next decade.
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PMID:Molecular therapy for renal diseases. 884 Sep 36

Insulin-dependent diabetic patients with nephropathy have a high risk of cardiovascular disease. Chronic inflammation is a part of the pathogenesis of atherosclerosis, and presently we have studied the relation between the inflammatory state, measured as levels of interleukin-6 and C-reactive protein and fibrinogen in diabetic nephropathy. Thirty-three insulin-dependent diabetic patients with diabetic nephropathy (urinary albumin excretion rate (AER) > 300 mg/24-h) and 22 patients with incipient diabetic nephropathy (AER 30-300 mg/24-h) were compared with 14 non-diabetic controls and 17 diabetic patients with normal AER (<30 mg/24-h). Fibrinogen was significantly higher in diabetic nephropathy than in non-diabetic controls and diabetic patients with normal AER (median 8.1, range (5.4-15.6) mu mol/l vs. 6.6 (5.0-12.1) mu mol/l, p < 0.05, and 6.2 (5.0-9.0) mu mol/l, p < 0.005, respectively), while C-reactive protein did not deviate between groups. Interleukin-6 was significantly elevated in all insulin-dependent diabetic patients (diabetic nephropathy (3.2 (1.0-14.5) pg/ml, p < 0.005), incipient nephropathy (3.7 (1.0-22.9) pg/ml, p < 0.005) and diabetic patients with normal AER (2.7 (1.0-9.0) pg/ml, p < 0.05) compared with nondiabetic controls (1.2 (1.0-6.2) pg/ml)). When fibrinogen was adjusted for interleukin-6, C-reactive protein or both, the level of fibrinogen was still higher in patients with diabetic nephropathy than in patients without nephropathy (p < 0.05), which suggests that inflammation is not the only mechanism that increases fibrinogen levels in patients with diabetic nephropathy.
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PMID:Elevated fibrinogen and the relation to acute phase response in diabetic nephropathy. 890 98


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