Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular involvement in rheumatoid arthritis (RA) is associated with a wide range of extra-articular complications. Damage to internal organs occurs through a widespread disorder of the microvasculature. Vasculitis, as an integral part of the disease process, is associated with immune system abnormalities. To evaluate the relationship between capillaroscopic abnormalities, extra-articular involvement and immunological alterations, serum levels of soluble CD4 (sCD4), CD8 (sCD8), tumour necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6) and soluble interleukin-6 receptor (sIL-6R) were determined by an enzyme-linked immunosorbent assay in 80 RA patients. In all patients with signs of extra-articular manifestations, severe or moderate changes in nailfold capillaroscopy were found. Serum levels of TNF-alpha, IL-6, sIL-6R and sCD4 were significantly higher in RA patients compared with 30 healthy subjects. RA patients with clinical signs of systemic vasculitis showed significantly higher levels of TNF-alpha and IL-6 compared with those without vascular involvement. Moreover, a significant correlation between sCD4 levels and the capillaroscopy findings was found. These results point to a pathogenic role of the cytokine network in rheumatoid vasculitis and further may suggest an important role of cellular immune activation in the pathogenesis of microvascular damage.
 ...
PMID:Cytokines and soluble CD4 and CD8 molecules in rheumatoid arthritis: relationship to systematic vasculitis and microvascular capillaroscopic abnormalities. 989 Jun 77

In this study, we used a mouse model to examine the role of the adaptive immune response in alveolar bone loss induced by oral infection with the human gram-negative anaerobic bacterium Porphyromonas gingivalis. Severe combined immunodeficient mice, which lack B and T lymphocytes, exhibited considerably less bone loss than did immunocompetent mice after oral infection, suggesting that lymphocytes contribute to this process. Bone loss after oral infection was decreased in mice deficient in major histocompatibility complex (MHC) class II-responsive CD4(+) T cells, but no change in bone loss was observed in mice deficient in MHC class I-responsive CD8(+) T cells or NK1(+) T cells. Mice lacking the cytokine gamma interferon or interleukin-6 also demonstrated decreased bone loss. These results suggest that the adaptive immune response, and in particular CD4(+) T cells and the proinflammatory cytokines that they secrete, are important effectors of bone loss consequent to P. gingivalis oral infection. The studies also reinforce the utility of the mouse oral infection model in dissecting the pathobiology of periodontal disease.
 ...
PMID:CD4(+) T cells and the proinflammatory cytokines gamma interferon and interleukin-6 contribute to alveolar bone loss in mice. 1033 84

Patients with Kaposi's sarcoma (KS) have a human herpesvirus-8 (HHV-8) load higher than patients without KS and present a CD8(+) T-cell activation with production of Th1-type cytokines both in tissues and peripheral blood mononuclear cells (PBMC). Because in tissues of KS patients detection of inflammatory cytokines (IC) can precede detection of HHV-8 DNA and because signs of immunoactivation and/or dysregulation can precede KS development, we investigated the effect of IC on HHV-8 infection. To achieve this goal, PBMC and purified cell populations from 45 patients with KS and 45 patients at risk of KS were analyzed for HHV-8 DNA and/or gene expression and for cell survival, growth, and phenotype before or after culture with or without the IC increased in KS. The results indicate that PBMC that are polymerase chain reaction (PCR)-positive at day 0 generally loose the virus upon culture. However, the presence of IC maintains HHV-8 DNA load in cultured cells. In addition, IC increase viral load to detectable levels in PBMC from serologically positive patients that were PCR-negative before culture. gamma Interferon is sufficient for these effects, whereas tumor necrosis factor and interleukin-6 have little or no activity. The increase of HHV-8 DNA by IC is observed after short-term (7 days) or long-term (28 days) culture of the cells and occurs in one or both of the two circulating cell types that are infected in vivo: B cells and monocytes. In both cases it is associated with lytic gene expression, suggesting that virus reactivation is one of the most likely mechanisms for the effect of IC on virus load. However, IC have also effects on the cells target of HHV-8 infection, because they increase B-cell survival and induce the growth and differentiation of monocytes into KS-like spindle cells with markers of endothelial macrophages. Because cells with markers of endothelial macrophages are present in blood and lesions from KS patients and are infected by HHV-8, these data may explain the high HHV-8 load associated with KS development and suggest that infected monocytes may carry the virus to tissues, transmit the infection, or differentiate in loco in spindle cells with endothelial macrophage markers.
 ...
PMID:Reactivation and persistence of human herpesvirus-8 infection in B cells and monocytes by Th-1 cytokines increased in Kaposi's sarcoma. 1036 Oct 99

To investigate neuropathological processes involved in HIV infection, a longitudinal analysis of central nervous system (CNS) changes was performed using the SIV-infected macaque model. Five animals were studied during the early phase and 13 during the asymptomatic and symptomatic phases. Histopathological analyses were performed on one cerebral fixed hemisphere whereas on the other frozen hemisphere in situ hybridisation, immunohistochemistry and RT-PCR were performed. Viral load was quantified by in situ hybridisation, CD4 and CD8 T cell infiltration by immunohistochemistry and mRNA cytokine expression (IL1beta, IL2, IL6, TNFalpha, IFNgamma and TGF-beta1) by semiquantitative RT-PCR. As reported for HIV-infected humans, the neuropathological analysis of SIV infected animals revealed four distinct lesion profiles: minimal changes, early encephalitis, leukoencephalopathy and encephalitis. No relationship was found between neuropathological findings, numbers of SIV replicating cells and T cell infiltration. CNS infection was found to be an early event characterised by glial activation, an increase in the level of IL1beta, TNFalpha and IL6 mRNA expression. During the asymptomatic and symptomatic phases, IL6 and IL1beta mRNAs increase coincided with gliosis and the development of myelin lesions. The absence of relationship between neuropathological findings and viral load suggests that cerebral lesions are caused by an indirect mechanism. Inflammatory cytokine pattern associated with severe lesions show the key role of glial activation in the SIV neuropathological process.
 ...
PMID:Viral load and neuropathology in the SIV model. 1041 13

Traumatic brain injury (TBI) induces local and systemic immunologic changes, release of cytokines, and cell activation. Perpetuation of these cascades may contribute to secondary damage to the brain. Therefore, the ability of the antiinflammatory mediator transforming growth factor-beta (TGF-beta) to downregulate intrathecal immunoactivation may be of fundamental value for diminishing the incidence and extent of secondary insults. In this study, the release of TGF-beta into cerebrospinal fluid (CSF) and serum of 22 patients with severe TBI was analyzed with respect to the function of the blood-brain barrier (BBB) for 21 days. Levels of TGF-beta in CSF increased to their maximum on the first day (median, 1.26 ng/mL), thereafter decreasing gradually over time. Median TGF-beta values in serum always remained within the reference interval (6.5 to 71.5 ng/mL). Daily assessment of the CSF-serum albumin quotient (QA) and of the CSF-serum TGF-beta quotient (QTGF-beta) showed a strong correlation between maximal QTGF-beta and QA, indicating a passage of this cytokine from the periphery to the intrathecal compartment across the BBB. However, calculation of the TGF-beta index (QTGF-beta/Q(A)) suggested a cerebral production of TGF-beta in 9 of 22 patients. Levels of TGF-beta could not be correlated with extent of initial injury by computed tomography (CT), CD4/CD8 ratios, acute lung injury, or clinical outcome as rated by the Glasgow Outcome Scale (GOS). Although increased levels of TGF-beta in CSF seem to parallel BBB function, a partial intrathecal production is suggested, possibly modulated by elevation of interleukin-6 (IL-6). Thus, TGF-beta may function as a factor in the complex cytokine network following TBI, acting as an antiinflammatory and neuroprotective mediator.
 ...
PMID:TGF-beta is elevated in the CSF of patients with severe traumatic brain injuries and parallels blood-brain barrier function. 1044 73

The availability of the myeloid hemopoietic growth factors (HGF) granulocyte- and granulocyte/macrophage-colony stimulating factor (G-CSF and GM-CSF) has enhanced the therapeutic index of high-dose chemotherapeutic antitumoral regimens (HDCT), as well as the rate of severe damage to immune competence. We investigated some immune functions before, during and after one course of HDCT for poor-risk breast cancer and compared the effects of G-CSF and GM-CSF on the immune recovery. They exerted different influences on the functions we examined and showed distinctive patterns of both qualitative and quantitative in vivo activities on the immune system. The main findings were that (a) granulocyte and lymphocyte recovery rates were faster in the patients receiving G-CSF; (b) looking at the lymphocyte compartment, this difference was restricted to the CD3(+)/CD8(+) and CD56(+) lymphocyte subsets; (c) the reconstitution rate of CD19(+) lymphocytes was slow in both groups; (d) at the end of follow-up HLA-DR expression by CD3(+) lymphocytes was higher in the GM-CSF group; (e) the lymphocyte proliferative capacity was restored at a faster rate in the GM-CSF group, whereas cytotoxic activities recovered better in the G-CSF group; (f) the early repopulating phase was characterized by higher interleukin-6 serum levels in the GM-CSF group. Overall, GM-CSF seemed to exert an earlier effect on all T lymphocyte subsets, preventing them from a complete drop during the long-lasting "nadir" of the cell count, whereas G-CSF appeared to boost them strongly, though a few days later, hastening their final recovery. The distinct pattern of the cytokine cascade induced by each factor, consistent with the different functional changes, seemed to account for the peculiarities of their immune modulations.
 ...
PMID:The induction of distinct cytokine cascades correlates with different effects of granulocyte-colony stimulating factor and granulocyte/macrophage-colony-stimulating factor on the lymphocyte compartment in the course of high-dose chemotherapy for breast cancer. 1047 3

We examined some immunological parameters, particularly cytokines and soluble factors in collagen diseases complicated with essential hypertension. We also investigated the effects of Nilvadipine on immunological parameters after treatment with this drug for six months. The frequency of helper/inducer T cells (CD4+ CD8- cells, CD4+ CD45RA- cells) decreased in the peripheral blood on a 6 month treatment with nilvadipine. There was a significant decrease of suppressor/inducer T cells (CD4+ 45RA+ cells), and an insignificant decrease of activated T cells (CD3+ HLA-DR+ cells) and memory T cells (CD45RA- CD45RO+ cells) after treatment. Before treatment with Nilvadipine, interleukin-1beta, tumor necrosis factor-a, and interleukin-6 levels increased higher in the patients than in healthy volunteers. However, interleukin-1beta and interleukin-6 concentrations tended to decrease after treatment with Nilvadipine. Besides, tumor necrosis factor-alpha decreased significantly after treatment. The soluble interleukin-2 receptor concentrations also showed a decreased tendency after treatment, although high concentrations were found in the patients before treatment. In contrast, soluble human leukocyte antigen-1 and soluble thrombomodulin levels showed no significant change after treatment. These results suggest that Nilvadipine inhibits the generation of cytokines derived from activated T lymphocytes. Nilvadipine, calcium antagonist, may be useful for inhibition of vascular complication in collagen diseases.
 ...
PMID:Effects of nilvadipine on cytokine-levels and soluble factors in collagen disease complicated with essential hypertension. 1051 35

We have previously described two cytotoxic T lymphocyte clones isolated from lymphocytes infiltrating a human major histocompatibility complex class II-/class I+, CD4+ cutaneous T cell lymphoma. These clones displayed a CD4+CD8dim+ (TC5) and CD4+ CD8- (TC7) phenotype and mediated a specific major histocompatibility complex class I-restricted cytotoxic activity toward Cou-LB autologous tumor cell line. Our studies were performed to elucidate the mechanism involved in T-cell-clone-mediated cytotoxicity and to determine the cytokine profile of both the lymphoma cell line and specific cytotoxic T lymphocyte clones. The results indicate that, despite surface expression of Fas receptor on Cou-LB and Fas ligand induction on TC5 and TC7 cell membranes, the CD4+ cytotoxic T lymphocyte clones do not use this cytotoxic mechanism to lyse their specific target. The TC7 clone uses instead a granzyme-perforin-dependent pathway. Furthermore, quantitative analysis of Th1 and Th2 cytokine mRNA expression in the cutaneous T cell lymphoma cell line as well as in TC5 and TC7 clones indicated that, whereas the tumor cells display a Th2-type profile (interleukin-4, interleukin-6, and interleukin-10), the cytotoxic T lymphocyte clones express Th1-type cytokines (interferon-gamma, granulocyte macrophage colony stimulating factor, and interleukin-2). In addition, preincubation of the tumor-infiltrating lymphocyte clones with autologous tumor cells induced their activation and subsequent amplification of the Th1-type response. These results indicate a direct contribution of the malignant cells in the Th1/Th2 imbalance observed frequently in cutaneous T cell lymphoma patients and suggest their potential role in depressed cell-mediated immunity. Identification of CD4+ Th1-type cytotoxic T lymphocyte clones, the tumor antigen they recognize, and optimization of their cytokine expression profile should be useful for the design of new immunotherapy protocols in cutaneous T cell lymphoma.
 ...
PMID:Cutaneous T cell lymphoma reactive CD4+ cytotoxic T lymphocyte clones display a Th1 cytokine profile and use a fas-independent pathway for specific tumor cell lysis. 1088 11

Glatiramer acetate (GA), represents an established treatment of relapsing/remitting multiple sclerosis (MS). The mechanisms responsible for the effect of GA are not fully understood. We generated GA-, myelin basic protein (MBP)- and purified protein derivative (PPD)-specific T cell lines from three MS patients and one healthy donor. The GA-specific lines were CD3+, CD4+, CD8- and produced tumor-necrosis-factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-4 (IL-4), interleukin-6 (IL-6) and interleukin-10 (IL-10) after stimulation with GA in the presence of irradiated peripheral blood mononuclear cells. MBP-specific T cell lines showed an identical phenotype and secreted TNF-alpha, IFN-gamma, IL-4, IL-10, but not IL-6. Co-culture experiments demonstrated, that GA-specific T cell lines have the capability to suppress the proliferation of MBP-specific T cell lines.
 ...
PMID:Glatiramer acetate (copolymer-1)-specific, human T cell lines: cytokine profile and suppression of T cell lines reactive against myelin basic protein. 1096 65

The contents of CD8(+), CD4(+)CD8(+), CD3(+)HLA-DR(+), CD8(+)INF-gamma (+) T cells, and natural killers (CD16(+)56(+)) and NK/T cells (CD16(+)56(+)CD3(+)) increase after 7-day culturing in the presence of interleukin-2. The number of apoptotic cells and cells in S-, and G(2)+M phases of the cell cycle also increased. Interleukin-6 predominantly induced proliferation of CD3(+)HLA-DR(+) T cells and G(2)+M mitotic cells.
 ...
PMID:Cytokine-induced differentiation and proliferation of human T lymphocytes in vitro: effects of interleukin 2 and interleukin 6. 1102 52


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>