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)

Hydroxychloroquine (HCQ), an antimalarial agent used to treat patients with autoimmune diseases, has been shown to suppress human immunodeficiency virus type 1 (HIV-1) replication in T cells and monocytes in vitro by inhibiting posttranscriptional modification of the virus. An initial randomized, placebo-controlled clinical trial conducted in 38 asymptomatic HIV-1-infected patients who had CD4+ counts between 200 and 500 cells/mm3 demonstrated that the amount of recoverable virus declined significantly in the HCQ group compared with the placebo group over the 8-week study period. These preliminary observations were expanded into a second 16-week clinical trial comparing the efficacy of HCQ with that of zidovudine (ZDV) in 72 asymptomatic HIV-1-infected patients with CD4+ counts between 200 and 500 cells/mm3. Patients were randomly assigned to receive either HCQ 800 mg/d (n = 35) or ZDV 500 mg/d (n = 37) for 16 weeks. No adverse reactions to the study medications were observed in either the HCQ or ZDV group. Patients in both groups had reduced levels of recoverable HIV-1 RNA in the plasma, reduced levels of cultured virus, and reduced levels of serum p24 antigen after the 16-week study period. However, no difference was noted in absolute CD4+ counts between the two groups. Interleukin-6 and serum immunoglobulin G levels were significantly reduced in the HCQ group but not in the ZDV group. These findings support the results of the previous clinical trial. Thus HCQ may be potentially useful in the treatment of patients with HIV-1 infection.
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PMID:Comparison of hydroxychloroquine with zidovudine in asymptomatic patients infected with human immunodeficiency virus type 1. 938 80

Induction of chemokine gene expression from peripheral blood mononuclear cells (PBMCs) stimulated by proinflammatory cytokines plays an important role in both wound repair and response to infectious agents. In the present study, we show that the proinflammatory cytokine interleukin-6 (IL-6) potently induced mRNA expression and secretion of the CC chemokine monocyte chemotactic protein 1 (MCP-1) in PBMCs. In addition, because human immunodeficiency virus (HIV) infection in vivo and in vitro has been shown to dysregulate the production of and/or the response to cytokines, PBMCs from both healthy uninfected and HIV-infected individuals were studied for their constitutive and IL-6-induced expression of MCP-1. No substantial differences were observed between the two groups of individuals. In addition, IL-6 upregulated MCP-1 expression in the promonocytic cell line U937 and in its chronically HIV-infected counterpart, U1. In these cell lines, IL-6 selectively induced MCP-1 and not other chemokines, including regulated upon activation normal T cells expressed and secreted (RANTES), macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and IL-8. IL-6 induction of MCP-1 was partially inhibited by hydrocortisone in U1 cells. Thus, IL-6 activates PBMCs to secrete MCP-1, a CC chemokine pivotal for monocyte recruitment in tissue and organs in which important inflammatory events occur.
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PMID:Interleukin-6 induces monocyte chemotactic protein-1 in peripheral blood mononuclear cells and in the U937 cell line. 941 93

Because malaria-stimulated cytokine production may have deleterious effects on human immunodeficiency virus type 1 (HIV-1) replication, the effects of Plasmodium falciparum antigens on HIV-1 replication were studied. Stimulation with malarial antigens significantly enhanced HIV-1 replication of HIV-1LAV and primary HIV-1 isolates (subtype A) in CD8-depleted peripheral blood mononuclear cells from naive donors. The malarial antigen-induced activation of HIV-1 was due to cellular activation as judged by the expression of cell activation markers and proliferative responses. While malarial antigen stimulation increased expression of tumor necrosis factor (TNF-alpha) and interleukin-6 (IL-6), only monoclonal antibodies (MAbs) to TNF-alpha inhibited malarial antigen-induced HIV-1 replication, whereas MAb to IL-6 had no effect. Malarial antigen increased HIV-1 replication by increasing viral mRNA expression and by activating long terminal repeat-directed viral transcription. These data suggest that P. falciparum infection can modulate HIV-1 pathogenesis by activating lymphocytes and stimulating viral replication through the production of cytokines.
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PMID:Plasmodium falciparum antigen-induced human immunodeficiency virus type 1 replication is mediated through induction of tumor necrosis factor-alpha. 946 33

Renal infiltration of human immunodeficiency virus type 1 (HIV-1)-infected monocytes might play an important role in the development of HIV-associated nephropathy (HIVAN). In the present study, we investigated the effects of cytokines produced by cultured human mesangial cells (HMC) and proximal tubular epithelial cells (PTEC) on HIV-1 expression in chronically HIV-1-infected promonocytes (U1 cells). Human mesangial cells constitutively secreted interleukin-6 (IL-6) but not tumor necrosis factor-alpha (TNF-alpha) into the culture medium, whereas PTEC constitutively secreted both IL-6 and TNF-alpha. Coculture of U1 cells with HMC or PTEC for 72 hours markedly stimulated HIV-1 expression, with the p24 antigen concentration in the coculture supernatants ranging from approximately 200 to 1850 pg/ml. The presence of anti-IL-6 antibody in the coculture medium nearly completely blocked HIV-1 expression in the HMC/U1 cell cocultures (P < 0.05). Anti-IL-6 antibody and anti-TNF-alpha antibody blocked HIV-1 expression in the PTEC/U1 cell cocultures by 40% and 53%, respectively (P < 0.05). Moreover, the combination of anti-IL-6 and anti-TNF-alpha antibodies additively reduced coculture HIV-1 expression by 87% (P < 0.05). We conclude that renal cell production of IL-6 and TNF-alpha might provide a potent stimulus for HIV-1 expression in HIV-1-infected monocytes that infiltrate the kidney, and that this may play an important role in the pathogenesis of HIVAN.
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PMID:Renal cell cytokine production stimulates HIV-1 expression in chronically HIV-1-infected monocytes. 950 3

This review attempts to put together the changes in the blood and bone marrow observed in those who are infected with human immunodeficiency virus (HIV). These are contribution of many published and unpublished data and experience on; blood counts, blood film and bone marrow films prepared and stained by MayGrunwald-Giemsa or Leishman stain. Some changes in haemostasis are also included. The salient changes are cytopaenias; leucopaenia, anaemia, thrombocytopaenia, and bone marrow hypoplasia, although the latter occurs, it is found in a minority of cases. Other changes include myelodysplasia, functionally defective cells, and enhanced bleeding tendency particularly in those with bleeding defects. There are also malignancies associated with HIV infection such as Kaposi's Sarcoma and malignant lymphomas. The pathogenesis of these events are multi-factorial, varied and involve; killing of cells by the virus, syncytial formation by the cells, destruction of the stem cells, immune and drugs effects. These mechanisms are modified by factors of viral, host environment and their interactions. Changes are commonly found in patients with acquired immunodeficiency syndrome (AIDS) but can be seen in some cases anytime during the course of the disease. Once developed the changes are progressive. The management of these complications remain individualised and symptomatic. Treatment trials with the haematopoesis growth factors, particularly colony stimulating factors are producing some encouraging results. However other cytokines, for example, interleukin-6 may be having untoward effect such as association with the causation of Kaposi's sarcoma and the malignant non-Hodgkin's lymphomas. While standard approaches to the management of the malignancies tend to be the practice, adjustments are usually necessary in most patients.
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PMID:Haematological changes in human immunodeficiency virus infection. Part I: Review article. 955 49

During immunodeficiency after sublethal haematoablative treatment, cytomegalovirus (CMV) infection interferes with haematopoietic reconstitution and can cause lethal bone marrow (BM) aplasia. The in vivo model of murine CMV infection has identified the BM stroma as the principal target site of CMV in the haematopoietic cord. The infected cell type is the reticular stromal cell which forms the stromal network and produces essential haemopoietins, such as stem-cell factor (SCF). The expression of SCF was found to be reduced in the infected stroma, but the stromal network was not disrupted and the number of infected stromal cells was too low to explain the functional deficiency. These facts call for a negatively regulating cytokine that is induced by the infection and that potentiates the direct effect of infection by down-regulating haemopoietins in uninfected bystander cells. Recent work has suggested that transforming growth factor (TGF)-beta1 might be the cytokine involved in CMV-induced BM aplasia. We show here that murine CMV indirectly induces the accumulation of mature TGF-beta1 in uninfected renal tubular epithelial cells and TGF-beta1 transcription in BM stromal cells, whereas infected renal glomerular and interstitial cells, hepatocytes and BM stromal cells do not coexpress mature TGF-beta1. Antiviral CD8 T-cell therapy prevented BM aplasia and also prevented the down-regulation of stromal SCF and interleukin-6 gene expression. Interestingly, however, the CD8 T cells did not preclude the up-regulation of mature TGF-beta1, but proved to be inducers of TGF-beta1 gene expression in BM stroma. These findings suggest that TGF-beta1 is not the mediator of BM aplasia.
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PMID:Evidence against a key role for transforming growth factor-beta1 in cytomegalovirus-induced bone marrow aplasia. 956 83

The relationship between Mycobacterium avium complex (MAC) bacteremia and proinflammatory cytokine and human immunodeficiency virus type 1 (HIV-1) RNA levels in AIDS was investigated. During a prospective study, blood samples were drawn monthly for mycobacterial cultures. Sera were available at baseline and onset of MAC bacteremia from 20 cases and at corresponding times from 19 controls. Mean interleukin-6 (IL-6) levels were 154% greater at the time of MAC bacteremia in cases than in controls. The IL-6 levels correlated with body temperature, serum tumor necrosis factor (TNF-alpha) levels, and alkaline phosphatase levels (P < or = .004 for each). Although TNF-alpha levels tended to rise more in MAC patients than in controls, the difference was not significant. However, among both cases and controls, serum TNF-alpha levels rose significantly from baseline to the time of last sample, irrespective of MAC infection (P = .015). Bacteremia was not associated with increased serum HIV-1 RNA levels. Thus, early MAC bacteremia is associated with increases in serum IL-6 levels, while TNF-alpha levels rise over time during advanced AIDS.
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PMID:Proinflammatory cytokine and human immunodeficiency virus RNA levels during early Mycobacterium avium complex bacteremia in advanced AIDS. 960 63

It is well known that cases with multiple myeloma reveal various clinical manifestations such as pancytopenia, hyperproteinemia, renal dysfunction, bone lesions, hypercalcemia and immunodeficiency. Recently, a few more clinical features associated with myeloma, such as salivary type hyperamylasemia and elevated serum C-reactive protein (CRP) concentration, have been reported. The elevation of CRP is thought to be related to interleukin-6 (IL-6) production by myeloma cells, because of identification of IL-6 as an autocrine and/or paracrine growth factor for myeloma cells. More recently, there have been several reports of cases with myeloma associated with hyperammonemia. This hyperammonemia is not considered to be due to liver dysfunction, because in most of these cases tests revealed normal hepatic function, and some cases showed different patterns of serum amino acid distribution than that associated with hepatic failure. However, there have been no apparent observations of ammonia production by myeloma cells. In this study, we used six human myeloma cell lines including KMS-18, which was recently established from a myeloma case associated with hyperammonemia. These lines were treated with MRA (mycoplasma removal agent) to observe ammonia production in vitro. They produced and released significantly higher levels of ammonia into culture medium than non-myeloma hematological cell lines or the HepG2 human hepatic carcinoma cell line. Although attempts to analyze the relative expression levels of the enzymes related to ammonia biosynthesis using the reverse transcriptase-polymerase chain reaction assay failed to detect any differences between these myeloma lines and other cell lines, in vitro excess ammonia production by the myeloma cells was confirmed and the relevance to clinical manifestations is discussed.
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PMID:In vitro excess ammonia production in human myeloma cell lines. 966 3

The initiation of antituberculosis treatment in patients with severe tuberculosis may be accompanied by clinical deterioration and even death before any improvement occurs. To investigate this phenomenon, newly diagnosed human immunodeficiency virus-negative adults with severe tuberculosis were followed for the first 42 days of standard short-course therapy. Clinical status, serum lactate, plasma cytokine, and plasma cytokine receptor levels were monitored on days 0, 3, and 7 and then weekly for up to 42 days. Following 7 days of antituberculosis therapy, a significant transient decrease in mean Karnofsky score (P < .001), a concomitant increase in serum lactate (P = .06), a decrease in patient weight (P = .02), and an increase in plasma tumor necrosis factor-alpha (TNF-alpha) concentrations (P = .04) were observed. Plasma levels of soluble interleukin-2 receptor, interferon-gamma, interleukin-6, and TNF-alpha receptor decreased over the 42-day study period. These observations suggest that increases in plasma TNF-alpha levels may be associated with clinical deterioration observed early in the treatment of severe tuberculosis.
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PMID:Selective increase in plasma tumor necrosis factor-alpha and concomitant clinical deterioration after initiating therapy in patients with severe tuberculosis. 969 49

The pineal neurohormone melatonin functionally synchronizes the organism with the photoperiod. It is now well recognized that melatonin also plays an important immunoregulatory role. T-helper cells bear G-protein coupled melatonin cell-membrane receptors and, perhaps, melatonin nuclear receptors. Activation of melatonin receptors enhances the release of T-helper cell type 1 (Th1) cytokines, such as gamma-interferon and interleukin-2, as well as of novel opioid cytokines which crossreact immunologically with both interleukin-4 and dynorphin B. Melatonin has also been reported to enhance the production of interleukin-6 from human monocytes. These mediators may counteract secondary immunodeficiencies, protect mice against lethal viral and bacterial diseases, synergize with interleukin-2 in cancer patients and influence hematopoiesis. Hematopoiesis is apparently influenced by the action of the melatonin-induced opioids on kappa-opioid receptors present on stromal bone marrow cells. Most interestingly, gamma-interferon and colony stimulating factors may modulate the production of melatonin in the pineal gland. A hypothetical pineal-immune-hematopoietic network is, therefore, taking shape. From the immunopharmacological point of view, a call is made for clinical studies on the effect of melatonin in viral disease including human immunodeficiency virus-infected patients and cancer patients. In conclusion, melatonin seems to be an important immunomodulatory hormone which deserves to be further studied to identify its relevance in immune-based diseases, its therapeutic indications, and its adverse effects.
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PMID:The photoperiod transducer melatonin and the immune-hematopoietic system. 971 19


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