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)

In order to characterize the expression of the viral interleukin-6 (vIL-6) homologue in various human herpesvirus 8 (HHV-8)-associated diseases, in situ hybridization and immunohistochemistry were applied to formalin-fixed specimens. These assays showed consistent expression of vIL-6 in primary effusion lymphomas and in a case of human immunodeficiency virus (HIV)-associated lymphadenopathy with a Castleman's disease-like appearance. In contrast, Kaposi's sarcoma specimens showed marked differences among specimens. In a consecutive series of specimens from the Johns Hopkins archives, vIL-6 expression was demonstrated in one of 13 cases. However, among 7 specimens selected from the AIDS Malignancy Bank because of their high levels of the T1.1 lytic transcript and virion production, vIL-6 expression was consistently demonstrated in infiltrating mononuclear cells and occasional spindle-shaped cells. Thus vIL-6 expression in clinical specimens correlates with other measures of the lytic viral cycle. Both assays generally give congruent results and are consistent with the possibility that vIL-6 expression plays a role in the pathogenesis of a variety of HHV-8-associated diseases.
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PMID:Heterogeneity of viral IL-6 expression in HHV-8-associated diseases. 1043 72

Cryptococcosis is an hematogenously disseminated meningoencephalitis during which the relationship between the disease severity and the immune response remains unclear. We thus analyzed, by enzyme-linked immunosorbent assay, proinflammatory (tumor necrosis factor alpha [TNF-alpha] and interleukin-6 [IL-6]) and anti-inflammatory (IL-10) cytokine levels in plasma at the time of diagnosis in 51 AIDS patients with culture-proven cryptococcosis. We used a murine model to determine the correlation between cytokine levels and fungal burden in blood and tissues and the kinetics of the immune response and of the formation of cerebral lesions. In AIDS patients, plasma TNF-alpha and IL-10, but not IL-6, levels were significantly higher in the case of fungemia or disseminated infection than in their absence, whereas the presence of meningitis had no influence on these levels. In mice, none of these cytokines were detected within the first day after inoculation. Later on, TNF-alpha and IL-10, but not IL-6, levels in plasma correlated significantly with the fungal burden in the blood and spleen but not the brain. In the brain, cytokine levels were low compared to those in other compartments, and tissue lesions and a degree of infection similar to those observed in humans were seen, further suggesting the relevance of this experimental model. Thus, AIDS patients with cryptococcosis produce an immune response that reflects the dissemination but not the meningeal involvement. This murine model of disseminated cryptococcosis can be used to investigate the pathophysiology of cryptococcosis and new therapeutic approaches.
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PMID:Cytokine profiles of AIDS patients are similar to those of mice with disseminated Cryptococcus neoformans infection. 1056 43

Oncostatin M (OSM), a cytokine first identified from activated monocytes and T lymphocytes, is one of the most potent autocrine growth factor for AIDS and Kaposi's sarcoma. Little is known about the effects of OSM on normal vascular cells. We thus exposed human aortic smooth muscle cells (hASMCs) to OSM, examined cell proliferation and morphology, and determined interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) expression. OSM had a weak antiproliferative effect. After a 4-day incubation with 100 ng/mL OSM, cell count decreased to 69+/-3% of control. However, OSM induced striking changes in hASMC morphology, characterized by a polyclonal shape, in contrast to the spindle morphological feature of control hASMCs. OSM stimulated the release of IL-6 by hASMCs in a dose-dependent way; after a 48-hour exposure, values were 8.5+/-0.7, 29.7+/-3.5, 50.9+/-4.4, and 73.8+/-7.6x10(3) U/mL (n=6) at OSM concentrations of 0, 1, 10, and 100 ng/mL, respectively. OSM induced marked expression of COX-2 protein and mRNA. Leukemia inhibitory factor had no effect on hASMCs, indicating that OSM effects on hASMCs were mediated by the OSM type II receptor and not by the leukemia inhibitory factor receptor. OSM used the JAK/STAT signaling pathway, as demonstrated by rapid phosphorylation of JAK1 and specific activation of STAT1. Interestingly, OSM acted in synergy with IL-1beta on IL-6 production and COX-2 expression. In conclusion, OSM is a novel regulator of human smooth muscle cell functions, acting in concert with IL-1beta, and OSM may play a role in major vascular diseases such as atherosclerosis.
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PMID:Oncostatin M induces interleukin-6 and cyclooxygenase-2 expression in human vascular smooth muscle cells : synergy with interleukin-1beta. 1059 Feb 38

Human herpesvirus 8 (HHV-8) has been causally linked to Kaposi's sarcoma (KS). There is significant homology between some HHV-8 genes and cellular genes including D-type cyclin (vCYC), G protein coupled receptor (vGCR), macrophage inflammatory proteins (vMIP-I, vMIP-II), bcl-2 (vBCL2), interferon regulatory factor-1 (vIRF1), interleukin-6 (vIL6), and complement-binding protein (vCBP). In this study, we analyzed expression of these viral homologs and HIV-1 Tat by reverse-transcriptase polymerase chain reaction (RT-PCR) coupled with Southern blot hybridization in AIDS-KS (AKS) tissue, classic KS tissue(CKS), and peripheral blood mononuclear cells, and phorbol ester (TPA)-treated and untreated HHV-8 positive lymphoma cells (BCBL1). While vCYC (AKS 6 of 6; CKS 3 of 3), vMIP-I (AKS 5 of 6, CKS 3 of 3), vBCL2 (AKS 6 of 6; CKS 3 of 3), and vIRF1 (AKS 5 of 6, CKS 3 of 3) transcripts were detected in both AKS and CKS, vGCR and HIV-1 Tat were expressed only in AKS samples (vGCR: AKS 3 of 6, CKS 0 of 3; Tat: AKS 4 of 6, CKS 0 of 3). vMIPII, vCBP, and vIL6 expression were not detected in any KS samples. Since vGCR expression is limited to AKS, it is possible that vGCR is activated by HIV-1 Tat. These results suggest that HIV-1 Tat may contribute to AKS pathogenesis through the tumorigenic and angiogenic effects of vGCR.
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PMID:Differential expression of the HHV-8 vGCR cellular homolog gene in AIDS-associated and classic Kaposi's sarcoma: potential role of HIV-1 Tat. 1066 20

Skeletal muscle tissue from SIV-infected macaques was previously found to contain abnormally high sulfate and low glutathione levels indicative of an excessive cysteine catabolism. We now confirm the peripheral tissue as a site of massive cysteine catabolism in HIV infection and have determined the urinary loss of sulfur per time unit. The comparison of the sulfate concentrations of the arterial and venous blood from the lower extremities of 16 symptomatic HIV+ patients and 18 HIV- control subjects (study 1) revealed (1) that the peripheral tissue of HIV+ patients with or without highly active antiretroviral therapy (HAART) releases large amounts of sulfate and (2) that plasma sulfate, thioredoxin, and interleukin-6 levels are elevated in these patients. A complementary investigation of 64 asymptomatic HIV+ patients and 65 HIV- subjects (study 2) revealed increased plasma sulfate levels in the asymptomatic patients. The analysis of the daily urinary excretion of sulfate and urea of another group of 19 HIV+ patients and 22 healthy HIV- subjects (study 3) confirmed (1) that HIV+ patients experience a massive loss of sulfur and (2) that this loss is not ameliorated by HAART. The sulfur loss of asymptomatic patients was equivalent to a mean loss of about 10 g of cysteine per day. If extrapolated, this would correspond to an alarming negative balance of approximately 2 kg of cysteine per year under the assumption that the normal sulfate excretion equivalent to approximately 3 g of cysteine per day is balanced by a standard Western diet. The abnormally high sulfate/urea ratio suggests that this process drains largely the glutathione pool.
AIDS Res Hum Retroviruses 2000 Feb 10
PMID:Massive loss of sulfur in HIV infection. 1071 Feb 8

The serum concentrations of inflammatory (Interleukin-1 beta, Tumor necrosis alpha, Interleukin-6) and regulatory cytokines (Interleukin twelve) have been studied in ten AIDS cachectic patients and compared to a control group. A cytokine imbalance, and peculiarly a significant increase in proinflammatory cytokines (Interleukin-1, Interleukin-6, Tumor necrosis Factor alpha) and a decrease in regulatory cytokines such as Interleukin-12 were found. A significant correlation resulted between weight loss and Interleukin-1 beta and 6. A negative correlation between Interleukin-1 and 12 was noted, indicating that this last cytokine has an important regulatory role also in advanced state of the disease.
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PMID:Proinflammatory and regulatory cytokine levels in AIDS cachexia. 1075 44

Interleukin-6 (IL-6), a major cytokine with diverse effects on cells mainly of the immune and hematopoietic systems, has been linked to several neurological disorders such as acquired immune deficiency syndrome dementia, multiple sclerosis, and Alzheimer's disease. Central nervous system (CNS)-specific expression of IL-6 caused neurodegeneration, massive gliosis, and vascular proliferation in transgenic mice. However, the effects of systemically circulating IL-6 and its receptor IL-6Ralpha on the CNS are unknown. IL-6Ralpha is the specific component of the IL-6 receptor system and hence an important co-factor of IL-6. IL-6Ralpha is bioactive in a membrane-bound and in a soluble (s) form. We investigated the effects of systemically elevated levels of either human IL-6 or human sIL-6Ralpha or both on the CNS of transgenic mice. Although IL-6 and sIL-6Ralpha single transgenic mice were free of neurological disease, IL-6/sIL-6Ralpha double-transgenic mice showed neurological signs, such as tremor, gait abnormalities, and paresis. However, these mice also frequently showed prominent general weakness probably because of the systemic effects of IL-6/IL-6Ralpha such as liver damage and plasmacytomas. IL-6/sIL-6Ralpha transgenic mice exhibited massive reactive gliosis. Lack of signs of neuronal breakdown versus ample astrogliosis suggested that astrocytes were selectively affected in these mice. There was neither vascular proliferation nor inflammatory infiltration. Ultrastructural analysis revealed blood-brain barrier (BBB) changes manifested by hydropic astrocytic end-feet. However, albumin immunohistochemistry did not reveal major BBB leakage. Our results indicate that increased and constitutive systemic expression of IL-6 together with its soluble receptor sIL-6Ralpha is less harmful to the brain than to other organs. The BBB remains primarily intact. IL-6/IL-6Ralpha, however, might be directly responsible for the selective activation of astrocytes.
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PMID:Astrocytic alterations in interleukin-6/Soluble interleukin-6 receptor alpha double-transgenic mice. 1107 9

Infection with human T cell leukemia virus type 1 (HTLV-1) can result in the development of HAM/TSP, a nonfatal, chronic inflammatory disease involving neuronal degeneration and demyelination of the central nervous system. Elevated levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1 observed in the cerebrospinal fluid of HAM-TSP patients suggest that cytokine dysregulation within the CNS is involved in neuropathogenesis. HTLV-1 infection and enhanced expression of TNF-alpha by microglial cells, astrocytes, and macrophages has been hypothesized to lead to the destruction of myelin and oligodendrocytes in the CNS. Although the association of HTLV-2 infection and development of neurological disease is more tenuous, HTLV-2 has also been found to be associated with peripheral neuropathies. To investigate the roles of HTLV Tax(1) and Tax(2) in the induction of cytokine disregulation in these cell types, we are currently developing gene delivery vectors based on human immunodeficiency virus type-1 (HIV-1) capable of stably coexpressing the HTLV-1 or -2 tax and eGFP reporter genes in primary human cells. Transduction frequencies of up to 50%, as assessed by eGFP expression, can be achieved in human monocyte-derived macrophages and in explanted cultures of human microglia. Preliminary data suggest that Tax(1) expression is sufficient to up-regulate the proinflammatory cytokine profile in explanted human microglial cells. Future experiments will compare and evaluate the effect of tax(1) and tax(2) gene expression on the cellular proinflammatory cytokine expression profile, as well as demonstrate the effects of transducing human fetal astrocytes and PBMC-derived macrophages.
AIDS Res Hum Retroviruses 2000 Nov 01
PMID:HTLV type 1 Tax transduction in microglial cells and astrocytes by lentiviral vectors. 1108 Aug 25

We studied 15 bone marrow biopsy specimens from patients with human immunodeficiency virus infection for detection of Kaposi sarcoma herpesvirus (KSHV/HHV-8) DNA sequences by a very sensitive and specific polymerase chain reaction (PCR) assay (with 3 different sets of primers). In addition, we used immunohistochemistry with antiviral interleukin-6 (vIL-6) and anti-latent nuclear antigen-1 (LNA-1) antibodies to localize the infected cells on tissue sections. Among the 15 samples, 6 had positive PCR results with the 3 sets of primers (orf26, orf72, orf75). Interestingly, in 2 of these 6 patients (both with Kaposi sarcoma) vIL-6 and LNA-1 were detected in mononuclear lymphoid cells but not in stromal cells of the bone marrow. The detection of vIL-6--positive lymphoid cells in bone marrow suggests a homing for HHV-8--infected elements in this tissue. The local release of vIL-6 may play some role in the plasmacytosis observed in bone marrow in the acquired immunodeficiency syndrome. HUM PATHOL 32:288-291.
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PMID:Detection and characterization of human herpesvirus-8-infected cells in bone marrow biopsies of human immunodeficiency virus-positive patients. 1127 37

The anti-HIV agent MAP30 (Momordica anti-HIV protein, 30 kDa) inhibits the proliferation of BC-2, an AIDS-related primary effusion lymphoma (PEL) cell line derived from an AIDS patient. BC-2 cells are latently infected with Kaposi's sarcoma-associated herpes virus (KSHV), also known as human herpes virus 8 (HHV8). We examined the effect of MAP30 on the expression of viral and cellular genes in BC-2 during latent and lytic states of the viral life cycle. By Northern analysis and RT-PCR, we found that MAP30 downregulates the expression of viral cyclin D (vCD), viral interleukin-6 (vIL-6), and viral FLIP (vFLIP), genes involved in cell cycle regulation, viral pathogenesis, and apoptosis. By pathway-specific cDNA microarray analysis, we found that BC-2 cells express high levels of egr-1, ATF-2, hsp27, hsp90, IkappaB, mdm2, skp1, and IL-2, cellular genes involved in mitogenesis, tumorigenesis, and inhibition of apoptosis in NFkappaB and p53 signaling pathways. These results define for the first time the specific cellular pathways involved in AIDS-related tumorigenesis and suggest specific novel targets for the treatment. Furthermore, we found that MAP30 downregulates the expression of egr-1, ATF-2, hsp27, hsp90, IkappaB, mdm2, and Skp1, while it upregulates the pro-apoptotic-related genes Bax, CRADD, and caspase-3. Thus, MAP30 modulates the expression of both viral and cellular genes involved in KS pathogenesis. These results provide valuable insight into the molecular mechanisms of MAP30 anti-KS action and suggest its utility as a therapeutic agent against AIDS-related tumors.
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PMID:Anti-HIV agent MAP30 modulates the expression profile of viral and cellular genes for proliferation and apoptosis in AIDS-related lymphoma cells infected with Kaposi's sarcoma-associated virus. 1157 62


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