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)

A cytogenetically normal man with severe aplastic anemia was treated with granulocyte colonystimulating factor (G-CSF), erythropoietin (EPO), cyclosporin A, anti-thymocyte globulin, and interleukin-6 (IL-6), which resulted in a gradual improvement in his neutrophil count and hemoglobin level. After 2 years of the therapy, monosomy 7 was detected during cytogenetic analysis of his bone marrow, which evolved during a period of 5 months into acute myeloblastic leukemia. An in vitro proliferation assay of cytokine responses showed that leukemic blasts were sensitive only to G-CSF, and not to EPO or IL-6. Although allogeneic bone marrow transplantation from an HLA-matched unrelated donor was carried out in the non-remission stage, the patient died of systemic fungal infection on day 25, without any evidence of hematological engraftment. As long-term use of cytokines and immunomo-suppressants in patients with severe aplastic anemia may induce or hasten the onset of a malignant transformation, careful attention must be paid to clonal evolution. Due to the poor prognosis of secondary myelodysplasia and leukemia, allogeneic bone marrow transplantation for such patients must be carried out early in the course of the disease.
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PMID:Transformation of severe aplastic anemia into acute myeloblastic leukemia with monosomy 7. 864 49

The two most common forms of X-linked adrenoleukodystrophy (X-ALD) are the cerebral forms (CER) with an inflammatory demyelinating reaction that resembles multiple sclerosis, and adrenomyeloneuropathy (AMN) which involves primarily the spinal cord and in which the inflammatory reaction is mild or absent. We found no significant association between the childhood cerebral form (CCER) or AMN and the human leukocyte (HLA) class I and Class II antigens including the class II DR2 haplotypes associated with multiple sclerosis. Inflammatory cytokine (tumor necrosis factor-alpha, interleukin-1 beta, interleukin-4, interleukin-6 and interferon-gamma) gene expression was increased in multiple sclerosis brain lesions, as has been reported previously, but much less so in CER brain lesions. These findings suggest that the pathogenesis of the inflammatory response in X-ALD differs from that in multiple sclerosis.
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PMID:Human leukocyte antigens and cytokine expression in cerebral inflammatory demyelinative lesions of X-linked adrenoleukodystrophy and multiple sclerosis. 914 52

The autoimmune basis for schizophrenia has been investigated for the last 60 years. Although numerous immune abnormalities have been reported, the current literature is viewed with much skepticism because most of the studies have failed to control for extraneous factors that may have influenced the findings. Principally, antipsychotic medication, duration of illness, and current clinical state (acutely psychotic or remitted) may considerably alter immune response, as may other factors such as nutritional status, substance abuse, and concurrent medical illness. We review recent studies that employed current diagnostic criteria and modern immunologic techniques. (These studies were located by use of a Medline search on the terms schizophrenia and psychosis, cross-referenced with immune abnormalities, lymphokines, antibodies, lymphocytes, HLA, and medication, and by perusing the reference lists in the articles found through this search.) Immune abnormalities that have been replicated in studies of schizophrenic patients include increased prevalence of antinuclear antibodies, decreased production of interleukin-2, and increased serum concentrations of interleukin-2 receptor and interleukin-6. Given the current importance of autoimmunity as an etiologic mechanism in several branches of medicine, further studies are needed, especially those having a longitudinal design and including drug-naive patients.
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PMID:Immune abnormalities in schizophrenia: evidence for the autoimmune hypothesis. 938 85

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.
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PMID:Effects of nilvadipine on cytokine-levels and soluble factors in collagen disease complicated with essential hypertension. 1051 35

The effects of physical therapy on immunological parameters were evaluated in 12 patients (8 males and 4 females, 69.2 +/- 9.0 years) with cerebrovascular diseases in a stable situation two to three months after the onset of stroke who entered in our hospital between 1994 and 1997. After a two-month physical therapy program, the proportions of helper-inducer T (Thi) cells and suppressor-inducer T (Tsi) cells were increased significantly and that of cytotoxic T (Tc) cells was decreased, although those of HLA-DR+, suppressor T (Ts) and activated T (Tac) cells were not changed. The antibody dependent cellular cytotoxicity (ADCC) was significantly increased, although natural killer (NK) cell activity was not changed. The serum levels of interleukin-2 receptor was significantly increased but those of interleukin-2, interleukin-6 and interleukin-12 were not changed. The serum levels of interleukin-10, interleukin-12 and tumor necrosis factor-alpha were not detectable, while interleukin-1beta was decreased in 2 patients and interleukin-10 was increased in 2 patients. These findings suggest that daily physical exercise may activate the immune system possibly through the cytokine network in patients with cerebrovascular diseases (CVD).
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PMID:Effects of physical therapy on cytokines and two color analysis-lymphocyte subsets in patients with cerebrovascular diseases. 1051 38

Dendritic cells (DCs) loaded with tumor antigens have the potential to become a powerful tool for clinical cancer treatment. Recently, the authors showed that a tumor-specific immune response can be elicited in culture via stimulation with autologous renal tumor lysate (Tuly)-loaded DCs that were generated from cytokine-cultured adherent peripheral blood mononuclear cells (PBMCs). Here, the authors show that immunomodulatory DCs can be generated directly from nonfractionated bulk PBMC cultures. Kinetic studies of DC differentiation and maturation in PBMC cultures were performed by monitoring the acquisition of DC-associated molecules using fluorescence-activated cell sorting analysis to determine the percentage of positive immunostained cells and the mean relative linear fluorescence intensity (MRLFI). Compared with conventional adherent CD14+ cultures, which have mostly natural killer, T, and B cells removed before cytokine culture, bulk PBMC cultures exhibited an early loss of CD14+ cells (day 0 = 78.8%, day 2 = 29.6% versus day 0 = 74%, day 2 = 75%) with an increase in yield of mature DCs (DC19- CD83+) (day 5 = 17%, day 6 = 21%, day 7 = 22% versus day 5 = 11%, day 6 = 15%, day 7 = 23%). Although a comparable percentage of DCs expressing CD86+ (B7-2), CD40+, and HLA-DR+ were detected in both cultures, higher expression levels were detected in DCs derived from bulk culture (CD86 = MRLFI 3665.1 versus 2662.1 on day 6; CD40 = MRLFI 1786 versus 681.2 on day 6; HLA-DR = MRLFI 6018.2 versus 3444.9 on day 2). Cytokines involved in DC maturation were determined by polymerase chain reaction demonstrating interleukin-6 (IL-6), IL-12, interferon-gamma, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-alpha mRNA expression by bulk culture cells during the entire 9-day culture period. This same cytokine mRNA profile was not found in the conventional adherent DC culture. Autologous renal Tuly (30 micrograms protein/10(7) PBMCs) enhanced human leukocyte antigen expression by DCs (class I = 7367.6 versus 4085.4 MRFLI; class II = 8277.2 versus 6175.7 MRFLI) and upregulated cytokine mRNAs levels. Concurrently, CD3+ CD56-, CD3+ CD25+, and CD3+ TCR+ cell populations increased and cytotoxicity against autologous renal cell carcinoma tumor target was induced. Specific cytotoxicity was augmented when cultures were boosted continuously with IL-2 (20 U/mL biological response modifier program) plus Tuly stimulation. These results suggest that nonadherent PBMCs may participate in enhancing DC maturation. Besides the simplicity of this culture technique, bulk DC cultures potentially may be used with the same efficiency as conventional purified DCs. Furthermore, bulk culture-derived DCs may be used directly in vivo as a tumor vaccine, or for further ex vivo expansion of co-cultured cytotoxic T cells to be used for adoptive immunotherapy.
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PMID:Immunomodulatory dendritic cells generated from nonfractionated bulk peripheral blood mononuclear cell cultures induce growth of cytotoxic T cells against renal cell carcinoma. 1068 41

Takayasu's arteritis is an inflammatory disease of the arteries that involves large vessels. The inflammatory lesions in Takayasu's arteritis originate in the vasa vasorum and are followed by cellular infiltration, mainly composed of T cells (gammadelta lymphocytes, cytotoxic T lymphocytes, T helper cells), but also of natural killer cells, dendritic cells, monocytes and granulocytes, invading the outer layer of the media and/or its neighbouring adventitia. At this stage, positive production of inflammatory cytokines and/or adhesion molecules around these areas is remarkable. According to data available--in Takayasu's arteritis--interleukin-6, interleukin-1 and RANTES are released in large amounts by infiltrating inflammatory cells within damaged tissue, as well as by circulating inflammatory cells, and very likely help maintain the aberrant immune activation, by promoting endothelial cells activation and by inducing lymphocyte infiltration. Although the nature of the antigen that triggers the auto-immune process is still unknown, the infiltrating T lymphocytes may recognize one or a few self-antigens processed and presented in association with HLA. A considerable percentage of patients with Takayasu's arteritis have immune complexes in sera; moreover, on peripheral blood lymphocyte, Fc receptors and antibodies reactive against human endothelial cells (AECA) have been detected. This observation raised the possibility that AECA might have a role in endothelial cell activation and expression of adhesion molecules, which will facilitate leukocyte traffic.
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PMID:Pathogenesis of Takayasu's arteritis. 1178 7

Multiple myeloma (MM) is a haematological malignancy characterised by the clonal expansion of malignant plasma cells within the bone marrow. It accounts for 10% of all haematological malignant diseases and 1% of all malignancies. The median age of patients at the time of the diagnosis is 70 years. The characteristic clinical features of MM are bone marrow failure, susceptibility to infections, bone pain, pathological bone fractures, hypercalcaemia, and renal failure. Though MM is currently incurable, the important progress in chemotherapy has resulted in an improvement in survival from a median of 7 months in the 1950-ies to about 3 years today. Advances in the diagnosis and in supportive treatment of infections, hypercalcaemia, and renal failure also contributed to the prolongation of survival. For decades, the gold standard of treatment had been oral melphalan alone or in combination with prednisolone. Combination chemotherapy has not improved overall survival (OS), but these regimens have led to the prolongation of event-free survival (EFS) and also to a better quality of life. High-dose chemotherapy with haemopoietic stem cell rescue resulted in a great improvement in EFS as well as OS. For those very few who have an HLA-compatible donor and are under 55, allogeneic bone marrow transplantation offers the best hope of survival but comes at a greatly increased risk of toxicity. There are conflicting data in the literature concerning the role of interferon-alpha; it seems to be able to prolong the duration of the plateau phase. Current treatment is moving towards an approach using sequential therapy. This involves induction therapy proceeding to high-dose chemotherapy with some form of stem-cell rescue. Bisphosphonates reduce hypercalcaemia, bone pain and can inhibit bone destruction. They also possess a direct antitumor activity. The better understanding of the pathomechanism of the disease gives the opportunity of the application of new therapeutic modalities such as antagonising the effect of interleukin-6 (IL-6), or idiotypic vaccination.
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PMID:[Therapy of multiple myeloma] 1205 Jul 24

The possibility for normal reproductive functioning in healthy, fertile women exists due to the presence of unique immunologic barriers, and also due to harmonic functioning of immunoregulatory mechanisms. It is believed that cytokines produced by activated lymphocytes, monocytes and macrophages, such as interleukin-1, interleukin-6, gamma-interferon and others, affect the processes of fertilization, development and implantation of the fertile egg in the uterus, and this may be a reason for habitual miscarriage and infertility. One of the most interesting and insufficiently studied trends of reproduction immunology undoubtedly remains the study of immune relationships between the mother and the fetus. Molecules of the major histocompatibility complex HLA G, E, C, expressed by trophoblast and placenta cells, play an important role in this relationship. Especially promising are studies of the role of the cytokine cascade and regulation of the expression of cytokine genes in the processes of fertilization and implantation of an early embryo, and also mechanisms regulating the invasion of trophoblast into the endometrium, which as a result ensures an adequate level of development of the fetoplacental complex. The study of the participation of the apoptosis process in the mechanisms of intrauterine development of the fetus and hypertrophic changes of the endometrium is interesting. Undoubtedly, further studies of the development of the fetus, the molecular-cellular specificities of different types of fetal tissues and the possibility of cellular transplantation as a new therapeutic technology in the case of habitual miscarriages, different forms of gestosis and intrauterine treatment of the fetus, will seem to be important.
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PMID:Interrelationships between Immune and Reproductive Systems in Human. 1268 44

Inflammation has been reported to play an important role in cardiac surgery under cardiopulmonary bypass due to systemic endotoxemia. In order to develop strategies against this injury in future we studied the combined effect of a number of inflammatory mediators in myocardial ischemia/reperfusion. Coronary sinus blood samples of ten patients undergoing coronary artery bypass graft surgery (CABG) were obtained at three time intervals (1) before onset of bypass (2) 30 min after cross clamp, and (3) 10 min after removal of cross clamp. The samples were subjected to evaluate levels of nitric oxide byproducts (nitrite and nitrate and citrulline), inflammatory cytokines (interleukin-2, interferon-gamma and interleukin-6), adhesion molecules, (CD62L and CD54), ratio of cell surface markers (CD4/CD8 and TCRalphabeta/gammadelta) cell activation markers (CD69 and HLA DR) and second messengers (protein kinase C, inositol 1,4,5 triphosphate and intracellular calcium levels). Ischemia and further reperfusion resulted in significant rise in nitrite and nitrate levels (p < 0.001), interleukin-6 (p < 0.01), CD62L (p < 0.001), CD69 (p < 0.05), protein kinase C (p < 0.001) and intracellular calcium (p < 0.001). A fall in CD4/CD8 ratio was observed on reperfusion. These changes during CABG show that ischemia/reperfusion leads to a release of an array of pro-inflammatory mediators of tissue injury, which could lead to pathophysiological changes. Hence the study suggests the need of some protective therapies against these inflammatory markers.
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PMID:Release of pro-inflammatory mediators during myocardial ischemia/reperfusion in coronary artery bypass graft surgery. 1284 27


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