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)

Familial hemophagocytic lymphohistiocytosis (FHL) is a frequently missed and almost uniformly fatal childhood disorder. It is characterized by fever, hepatosplenomegaly, cytopenia, coagulopathy, and hypertriglyceridemia. The pathogenesis of FHL is not known but the above clinical and laboratory findings are compatible with reported in vitro and in vivo effects of several inflammatory cytokines. We measured circulating interferon-gamma (IFN-gamma), tumor necrosis factor/cachectin (TNF), and interleukin-6 (IL-6) in nine children with FHL. During active disease, elevated IFN-gamma was detected in seven of seven children, TNF in six of six, and IL-6 in two of six children studied. Thus, important inflammatory cytokines are augmented in active FHL and may contribute to the pathogenesis of the disease. Soluble CD8 was also increased in seven of seven children, which suggests a pathophysiologic importance of cytotoxic T lymphocytes. Because FHL appears to be associated with a systemic hypercytokinemia, our results also indicate that studies of FHL may contribute to the understanding of cytokine effects in vivo. Moreover, FHL is a hereditary disorder, suggesting that the hypercytokinemia is caused by a genetic defect in cytokine regulation.
Blood 1991 Dec 01
PMID:Hypercytokinemia in familial hemophagocytic lymphohistiocytosis. 195 80

Defined by histological criteria, Castleman's disease (CD) is a clinically and histologically heterogeneous syndrome. The functional status of immune cells in affected tissues may vary between the different forms of the disease. To address this question, the expression of cytokine genes in eight CD lymph nodes was analyzed by in situ hybridization. Two lymph nodes were taken from patients with a localized form of the disease associated with systemic manifestations, two from patients with a localized form without systemic symptoms, and four from patients with a multicentric form. Five lymph nodes exhibiting a benign follicular hyperplasia were used as controls. The interleukin-6 (IL-6) gene was expressed at a very high level in two cases: the two localized forms of CD associated with systemic manifestations. IL-6 gene overexpression occurred inside follicles of these lymph nodes. The morphology of follicular cells hybridizing with the IL-6 probe or labeled with an anti-IL-6 monoclonal antibody suggested that follicular dendritic cells expressed the IL-6 gene. In contrast, no IL-6 gene expression was detected inside follicles of the six other CD lymph nodes or of the five control lymph nodes. In interfollicular areas, IL-6 gene-expressing cells were detected in all lymph nodes by both in situ hybridization and immunohistochemistry. In CD lymph nodes, positive cells were located outside sinuses, in close contact with blood vessels and plasma cells. This distribution was clearly different from that observed in control lymph nodes, in which IL-6 gene-expressing cells were present inside sinuses. A similar difference between CD and control lymph nodes was observed for the distribution of IL-1 beta and IL-1 alpha gene-expressing cells in interfollicular areas. The morphology of interfollicular IL-6-producing cells was heterogeneous, consistent with that of macrophages, interdigitating cells, lymphocytes, and endothelial cells, and different from that of plasma cells. Taken together these results show that CD is consistently associated with a particular pattern of IL-6 gene expression in interfollicular areas whereas elevated IL-6 gene expression inside follicles only occurs in the localized form of the disease associated with systemic manifestations. The variable pattern of IL-6 gene expression as well as the clinical and histologic heterogeneity of CD indicate that different immune mechanisms may be involved in the different forms of this disease.
Blood 1991 Dec 01
PMID:Interleukin-6 gene expression in Castleman's disease. 195 81

The influence of sedative and anxiolytic benzodiazepines on human monocyte function was assessed in 11 patients undergoing anesthesia prior to control endoscopy of the urinary tract. A single i.v. injection of 0.08 mg/kg midazolam induced a marked and delayed inhibition of the lipopolysaccharide-induced production of interleukin-1 beta, tumor necrosis factor-alpha and interleukin-6 by monocytes isolated from peripheral blood. Corticosteroids were not responsible for the observed immunosuppression. These studies demonstrate that, when administered in man, benzodiazepines markedly alter the capacity of monocytes to synthetize major mediators of the host inflammatory response.
J Neuroimmunol 1991 Dec
PMID:Benzodiazepine anesthesia in humans modulates the interleukin-1 beta, tumor necrosis factor-alpha and interleukin-6 responses of blood monocytes. 195 61

The biologic in vivo effects of recombinant human interleukin-3 (rhIL-3) were assessed in a phase I clinical study of 30 patients with advanced malignancy. On day 1 rhIL-3 was administered by a single intravenous (IV) bolus injection, followed by subcutaneous (SC) injections once daily from day 2 to 15; at least three patients were treated at each dose level (60, 125, 250, and 500 micrograms/m2). A transient decrease of eosinophil and monocyte counts was observed immediately after IV injection of rhIL-3, whereas the neutrophil count remained unaffected. Total WBC counts and neutrophil counts increased dose dependently up to threefold, whereas a 10-fold to 50-fold rise was observed in levels of circulating eosinophils and basophils. Platelet counts increased up to twofold. Patients developed moderate increases of serum levels of soluble interleukin-2 receptors, beta 2-microglobin, and immunoglobulin M (IgM), and of the acute phase reactants, C-reactive protein (CRP), fibrinogen, and haptoglobin. An increase in interleukin-6 (IL-6) serum levels was detected in patients treated by IV bolus rhIL-3. The serum half-life of IV injected rhIL-3 was 20 +/- 3 minutes; after SC administration, 210 +/- 15 minutes. Administration of rhIL-3 was generally well tolerated, with mild fever, headache, and local reactions at the injection site being the most frequent side effects. The primary course of the underlying malignant diseases was not significantly altered by administration of rhIL-3. The results indicate that rhIL-3 acts in vivo as a multilineage hematopoietic growth factor and a weak inflammatory mediator that may be used successfully to improve states of hematopoietic failure.
J Clin Oncol 1991 Dec
PMID:Biologic effects of recombinant human interleukin-3 in vivo. 196 May 53

N2-[(N-Acetylmuramoyl)-L-alanyl-D-isoglutaminyl-N6-stearoyl-L-lysine [MDP-Lys(L18), romurtide] is an immunopotentiating substance. In addition to neutrophilic leukocytosis, the effects previously found after the administration of this compound in both mice and humans were thrombocytosis and elevated levels of colony-stimulating factor (CSF) in peripheral blood. Although the exact mechanism of thrombopoiesis is not yet known, evidence has been accumulating that interleukin-6 (IL-6) plays an important role in the maturation of megakaryocytes, and the administration of IL-6 has been reported to induce a significant increase in blood platelets associated with promotion of megakaryocyte maturation. We measured the IL-6 levels in the culture supernatants of peripheral blood mononuclear cells (PBMCs), adherent cells and nonadherent cells in the presence of romurtide. Significant augmentation of IL-6 from PBMCs and adherent cells, but not nonadherent cells, was observed in the presence of romurtide in vitro.
Res Commun Chem Pathol Pharmacol 1990 Dec
PMID:Production of interleukin-6 from macrophages by MDP-Lys (L 18), romurtide. 209 10

Cells that produce interleukin-6 (IL-6) require the presence of signaling molecules since this cytokine is not normally constitutively expressed. It is now established that astrocytes produce IL-6; however, the precise inducing molecules and the kinetics of their action have not yet been clearly identified. In the current study, we show that either interleukin-1 beta (IL-1 beta) or tumor necrosis factor-alpha (TNF-alpha) exert a strong inducing signal for IL-6 in primary rat astrocytes. When the two cytokines are added together the response is synergistic, suggesting that each cytokine may induce IL-6 gene expression by different pathways. Interferon-gamma (IFN-gamma) does not affect IL-6 expression although if it is added in conjunction with IL-1 beta, an augmented induction of IL-6 occurs. In addition to the cytokines, bacterial lipopolysaccharide (LPS) and the calcium ionophore, A23187, induce IL-6 expression. IL-6 expression can be blocked by the glucocorticoid analogue, dexamethasone. IL-6 induction by LPS/Ca2+ ionophore is more sensitive to the suppressive effects of dexamethasone than is IL-6 induction by TNF-alpha/IL-1 beta. Cycloheximide (CHX), an inhibitor of protein synthesis, markedly increased levels of IL-6 mRNA in both unstimulated and stimulated astrocytes, indicating that ongoing protein synthesis is not required for astrocyte IL-6 gene expression. We propose that astrocyte-produced IL-6 may have a role in augmenting intracerebral immune responses in neurological diseases such as multiple sclerosis (MS), AIDS dementia complex (ADC), and viral infections. These diseases are characterized by infiltration of lymphoid and mononuclear cells into the central nervous system (CNS), and intrathecal production of immunoglobulins. IL-6 may act to promote terminal differentiation of B cells in the CNS, leading to immunoglobulin synthesis.
J Neuroimmunol 1990 Dec
PMID:Induction and regulation of interleukin-6 gene expression in rat astrocytes. 212

Polymyalgia rheumatica and giant cell arteritis are diseases which are characterized by a brisk acute phase response. Cytokines, principally interleukin-1 and interleukin-6, are thought to mediate the release of acute phase proteins from hepatocytes. Employing a sensitive bioassay based on the hybridoma growth factor properties of interleukin-6, we investigated its levels in sequential sera obtained from 15 initially untreated patients with PMR/GCA. We found that interleukin-6 activity was significantly elevated in all untreated patients. Although there was a significant decline in its levels after successful steroid therapy, seven patients continued to have raised serum levels of interleukin-6 for up to 6 months after initiation of treatment. Activated endothelial cells are a potent source of interleukin-6 and its persistence in the circulation may be taken as evidence of continuing disease activity. What is not explicable is the normalization of the acute phase response soon after the commencement of steroid therapy when circulating levels of interleukin-6 are still high. This suggests that steroids may be having additional effects on hepatocyte function.
Br J Rheumatol 1990 Dec
PMID:Interleukin-6 in serum of patients with polymyalgia rheumatica and giant cell arteritis. 212 60

The regulation of class I and class II HLA expression in human thyroid follicular cells was studied in vitro. Tumour necrosis factor-alpha (TNF-alpha) enhanced the expression of class I antigen on thyrocytes, but these cytokines had little effect on the expression of class II antigen. Interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) did not affect class I and class II antigen expression. The combination of interferon-gamma (IFN-gamma) with TNF-alpha or IL-1 beta enhanced the induction of class I and class II antigens, compared with the effect of IFN-gamma alone. Neither class I nor class II expression was induced by IL-6 alone or in combination with IFN-gamma. These findings suggest that TNF-alpha and IL-1 beta may have an important role in inappropriate expression of HLA antigens on thyrocytes in thyroid gland.
Clin Exp Immunol 1990 Dec
PMID:Cytokine regulation of HLA on thyroid epithelial cells. 212 59

It is now generally recognized that interleukin-6 (IL6) is one of the cytokines that mediate the various nonspecific host defense responses to infectious pathogens. Among its now well-demonstrated effects on systemic administration are fever and acute-phase proteinemia. These effects are also activated by the cytokine, IL1, and it has been shown that they are modulated in the preoptic-anterior hypothalamus (POA). This study was undertaken to determine whether this brain region similarly drives the febrile and proteinemic responses to IL6. We compared, therefore, these responses of conscious guinea pigs to human recombinant (hr)IL6 administered intravenously (IV) and into the POA. hrIL6 given IV was not pyrogenic at 1 microgram/kg, caused low-grade, dose-independent fevers (0.4 +/- 0.1 degree C) at 5-20 micrograms/kg, and dose-related fevers at 50 and 100 micrograms/kg (0.6 +/- 0.0 and 0.9 +/- 0.1 degree C, respectively). However, all doses of hrIL6 induced elevations in the plasma levels of ceruloplasmin (as an indicator of acute-phase proteins), albeit not in a dose-dependent manner. Indomethacin (10 mg/kg, injected intramuscularly 20 min before hrIL6) abolished the febrile response, but did not prevent the rise in plasma ceruloplasmin levels. Fever and ceruloplasminemia were also evoked by 50 and 100 ng of hrIL6 injected into the POA (1 microliter bilaterally), but not by 25 ng. These results indicate that the inductions of fever and plasma ceruloplasmin by IL6 are, like those of IL1, modulated in the POA, albeit the effective doses are much higher than those of IL1.
Brain Res Bull 1990 Dec
PMID:Neuromodulation of acute-phase responses to interleukin-6 in guinea pigs. 212 80

Human T cell hybridomas were constructed by somatic cell fusion in order to dissect molecular heterogeneity of human macrophage activating-factors (MAF). Two stable human hybridoma supernatants contained MAF activity capable of inducing human monocytes tumoricidal without the help of bacterial lipopolysaccharide (LPS). These supernatants in the presence of LPS could also render mouse macrophages tumoricidal. In contrast, recombinant and natural human interferon-gamma (Hu-IFN-gamma) activated human monocytes, but not mouse peritoneal macrophages. The supernatants from the two clones could neither support the growth of human-granulocyte-macrophage colony stimulating factor/human-interleukin-4-dependent (Hu-GM-CSF/Hu-IL-4) cell lines, such as AML 193 and TALL-101, nor stimulate the proliferation of human-interleukin-2-dependent human cell line and lectin-stimulated lymphoblast, which are responsive to human-interleukin-2 and human-interleukin-4. Rabbit or murine antibodies against human-interferon-gamma (Hu-IFN), human-granulocyte-macrophage colony stimulating factor, human interleukin-1 alpha, human-interleukin-1 beta, human-interleukin-6, human-tumour necrosis factor (Hu-TNF), human-lymphotoxin and human-macrophage migration inhibitory factor (Hu-MIF) could not absorb MAF activity. MAF activity in the hybridoma supernatants is associated with the two polypeptides of molecular weights of 70,000-80,000 and 20,000-30,000 daltons, as determined by gel filtration. These results indicate decisively that novel MAF molecule(s) is secreted by human T cell hybridomas.
Clin Invest Med 1990 Dec
PMID:Constitutive production of novel macrophage-activating factor(s) by human T cell hybridomas. 212 37


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