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)

Chronic urticaria remains one of the major unsolved clinical problems in dermatology. My group has employed an integrated experimental approach in order to shed light on the pathophysiology and treatment of this group of disorders. Using delayed pressure urticaria as a model, evidence has emerged of the role of eosinophil major basic protein (MBP) and of interleukin-6 (IL-6) as important molecular mediators, possibly explaining the poor response to H1 antihistamines. Our recent work in chronic idiopathic urticaria has led to identification of a circulating greater than 100 kD factor which causes wealing following intradermal injection and which releases histamine from normal leukocytes in vitro. Further characterisation confirmed that this skin and histamine releasing reactivity is due mainly to an IgG anti-IgE autoantibody. That this autoantibody is functionally significant is supported not only by its ability to release histamine and cause local wealing, but also by the results of removal by plasmapheresis which we have shown to cause clinical improvement in seven out of eight patients with severe unremitting chronic urticaria. It is concluded that chronic 'idiopathic' urticaria is an autoimmune disease due, in most patients, to a functionally significant IgG anti-IgE autoantibody. Immunotherapy offers the best long-term prospects of relief in severe unremitting cases.
 ...
PMID:Urticaria: new molecular insights and treatments. The Parkes Weber Lecture 1991. 137 92

We used a BALB/c model of passive cutaneous anaphylaxis (PCA), an IgE-mediated, mast cell-dependent reaction, to demonstrate the early production of the proinflammatory cytokine interleukin-6 (IL-6) mRNA and protein product. Northern blot analysis detects IL-6 mRNA 1, and 2 hours after antigen challenge (dinitrophenyl30-40 human serum albumin [DNP30-40-HSA]) and in situ hybridization reveals that it is primarily cells with round-to-oval nuclei within the dermis (1 to 3 per high-power field) expressing IL-6 mRNA. Immunohistochemistry revealed perinuclear and cytoplasmic staining for immunoreactive IL-6 in mononuclear dermal cells and also cells within the basal keratinocyte layer. Injection of recombinant murine IL-6 (rmIL-6) either systemically or locally during antidinitrophenyl IgE skin sensitization resulted in increased vasopermeability at the PCA site after DNP30-40-HSA. However, this increased permeability was not associated with a change in the character of the cellular infiltrate at the PCA site 8 hours later. Although the specific role of IL-6 in the generation of the allergic response remains unknown, its detection during PCA unequivocally demonstrates that IL-6 be considered one of the mediators identified in inflammation that follows allergic reactions.
 ...
PMID:Passive cutaneous anaphylaxis in mouse skin is associated with local accumulation of interleukin-6 mRNA and immunoreactive interleukin-6 protein. 143 Jul 7

We have previously demonstrated the production of tumor necrosis factor alpha (TNF) and interleukin-6 (IL-6) by alveolar macrophages (AM) from allergic asthmatics developing a late asthmatic reaction after bronchial allergen challenge. In order to explain the modalities of this monokine synthesis, we tested in vitro the effect of an IgE-dependent stimulation on blood monocytes (BM) and AM from control and asthmatic subjects. TNF and IL-6 secretions were evaluated in 24-h supernatants by radioimmunoassay and by the 7TD1 cell proliferation test, respectively. AM from allergic asthmatics secreted spontaneously higher concentrations of TNF and IL-6 than did BM or AM from control subjects. BM from asthmatics also produced spontaneously increased levels of TNF, but at a lesser degree than did AM. The addition of anti-IgE induced a significant increase of TNF and IL-6 secretions by mononuclear phagocytes from control subjects only after previous sensitization with IgE-rich medium. In contrast, the direct stimulation by allergen or anti-IgE of AM and BM from asthmatics enhanced significantly the production of TNF and IL-6 when compared with cells cultured in medium alone. In these conditions, IgE-dependent activation of cells from allergic asthmatics compared with those from control subjects increased monokine production in a similar manner. Costimulation by recombinant human interferon gamma and IgE-dependent triggering had a synergistic effect on TNF production, but it had only an additive action on IL-6 synthesis (respective increase index: 9.8 compared with 2.9 and 9.8 compared with 2.1, respectively, for BM from control and asthmatic subjects).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Tumor necrosis factor alpha and interleukin-6 production by human mononuclear phagocytes from allergic asthmatics after IgE-dependent stimulation. 151 61

The aim of the present study was to assess the significance of IgE and interleukin-6 (IL-6) in paired CSF and serum of patients with viral and bacterial infections of the central nervous system. The results suggest that the detection of IL-6 and IgE in CSF is an useful marker for monitoring course and prognosis of these patients.
 ...
PMID:Cerebrospinal fluid interleukin-6 and IgE in bacterial and viral meningitis. 158 Feb 6

The effect of disodium cromoglycate (DSCG) upon human immunoglobulin (Ig) isotypes and IgG subclasses production by purified B cells was studied. DSCG enhanced IgM, IgG1, IgG2, IgG3, IgG4 and IgA production in a dose-dependent fashion, while DSCG failed to induce IgE production at any concentrations tested by purified B cells. When B cells were separated into small resting and large activated B cells, DSCG failed to induce Ig production from small resting B cells in the presence or absence of Staphylococcus aureus Cowan strain I (SAC). In contrast, in large activated B cells DSCG significantly enhanced all types of Ig production (two-to threefold), especially IgG4 production (seven-to 11-fold), except IgE, which large B cells did not produce. The enhancement of IgG subclass production was not subclass switching, since DSCG failed to enhance IgG1 production in B cells depleted of surface IgG1+ cells (sIgG1+ cells). Similarly, DSCG did not enhance IgG2, IgG3 or IgG4 production from sIgG2-, sIgG3- or sIgG4- B cells, respectively, Interleukin-4 (IL-4) or interleukin-6 (IL-6) also enhanced Ig production except IgG4 from large activated B cells. The enhancing effect of DSCG was not mediated by IL-4 or IL-6 since anti-IL-4 or anti-IL-6 antibody failed to block the DSCG-induced enhancement. DSCG also enhanced IgG2 and IgM production from human B-cell lines GM-1500 and CBL, respectively. These results suggest that DSCG directly and preferentially stimulates activated B cells which are producing Ig and, in addition, enhances their Ig production.
 ...
PMID:Disodium cromoglycate enhances ongoing immunoglobulin production in vitro in human B cells. 190

Intravenous injection of goat antibodies to mouse IgD (GAMD) into BALB/c mice has been shown to induce vigorous T-cell dependent immunoglobulin responses, particularly of the IgG1 and IgE isotypes. We have confirmed these findings and show that IgA responses are also triggered in this model. Since the study of IgE regulation in allergic individuals is concerned with secondary and subsequent T- and B-cell responses, we boosted GAMD-primed mice with goat antibodies to IgE or IgA in an attempt to specifically retrigger IgE- and IgA-bearing memory B cells. However, we found that secondary IgG1, IgE and IgA production could be elicited equally well by either antibody preparation or by normal goat IgG (GIg). As with the primary response, GIg primed and boosted mice produced very low or undetectable IgG1, IgE and IgA responses. These data suggest that GAMD is very efficient at priming T cells specific for GIg epitopes and that once primed they can be readily re-triggered by GIg. Spleen cells taken 7 days after boosting GAMD-primed mice were found to spontaneously produce much higher levels of interleukin-6 (IL-6) in culture than cells from unboosted or GIg primed and boosted mice. In contrast to primary responses, where IgE levels return to background (less than 40 ng/ml) very quickly, circulating IgE levels in boosted mice initially declined before reaching a plateau level (approximately 1 microgram/ml) which was maintained for at least 148 days. IgG1 and IgA levels continued to fall over this same time period. Mice which had been primed (but not boosted) 10 months earlier were all found to have detectable IgE in their blood, despite the fact that following priming IgE becomes undetectable within 2-3 weeks. Since only a part of the IgE response was directed towards the antigen (GIg), these observations suggest the possibility that B cells initially primed to make IgE can be non-specifically retriggered in vivo.
 ...
PMID:Secondary immunoglobulin responses of BALB/c mice previously stimulated with goat anti-mouse IgD. 202 42

The cross-linkage of high affinity Fc epsilon receptors (Fc epsilon RI) on mast cells and basophils is central to the induction of allergic inflammatory responses. As a result of such cross-linkage, mast cells secrete a variety of preformed biologically active substances, such as histamine, and newly synthesized arachidonic acid metabolites. Here we show that cross-linkage of Fc epsilon RI on a series of nontransformed murine mast cell lines, or treatment of these cells with calcium ionophores, stimulates increased messenger RNA levels and secretion of a group of lymphokines classically produced by a subset of murine T cell lines (TH2 cells). These factors include interleukin-3 (a mast cell growth factor)s interleukin-4 (an IgE 'switch factor'), interleukin-5 (an eosinophil differentiation factor) and interleukin-6 (a factor controlling immunoglobulin secretion). The production of these polypeptide factors by mast cells may have great importance in the induction of allergic and anti-parasite inflammatory responses.
 ...
PMID:Mast cell lines produce lymphokines in response to cross-linkage of Fc epsilon RI or to calcium ionophores. 246 65

The synovial fluid of patients with rheumatoid arthritis (RA) contains a biologically active factor which has the ability to replace T cells for the induction of antibody secretion by human blood lymphoid cells stimulated by pokeweed mitogen (PWM) in vitro. This factor, which will be referred to as RA-SF (synovial fluid), also has the capacity to act as a B cell-stimulatory factor of mouse splenic lymphocytes in the presence of lipopolysaccharide (LPS). Using a test system developed for the definition of interleukin 4 (IL-4), which is a B cell-stimulating lymphokine which preferentially activates the synthesis of selected Ig classes in mouse lymphoid cells, we have shown that RA-SF has properties similar to IL-4 in that it induces differentiation of antibody secretion in the LPS-pretreated mouse cell, but unlike IL-4, which gives IgG1 and IgE, it selectively induces IgG2b synthesis. The present study demonstrates that RA-SF has a biological activity that is reminiscent of other B cell-stimulating mouse lymphokines, but it is biologically distinct from IL-2, IL-4, and IL-5. Recent data also indicate that it is distinct from gamma interferon (IFN-gamma). Therefore, we conclude that the biological activity of RA-SF has properties in common with a T-cell replacing (TRF) and B-cell differentiation factor (BCDF) and probably represents yet another biological activity which so far lacks an experimental counterpart. The relevance of this factor for autoantibody synthesis is discussed.
 ...
PMID:Biological characterization of T cell-replacing factor in the synovial fluid of rheumatoid arthritis patients. 326 Jun 84

A 43-year-old woman with a 10-year history of bronchial asthma developed marked peripheral blood eosinophilia and symptoms of vasculitis. A diagnosis of Churg-Strauss syndrome (CSS) was made, and her symptoms were successfully treated with low-dose prednisolone. Serum rheumatoid factors (RF) of both IgG and IgM, but not IgA or IgE, subclasses transiently appeared in accordance with the vasculitic phase. Serum interleukin-6 (IL-6) levels also transiently increased in this phase and the peak level was reached just prior to the maximum of RF elevation, suggesting the role of IL-6 as an inducer of RF. RF and IL-6 seemed to be involved in the pathogenesis of the vasculitis in this patient.
 ...
PMID:IgG and IgM rheumatoid factor levels parallel interleukin-6 during the vasculitic phase in a patient with Churg-Strauss syndrome. 749 76

Mast cells produce a number of cytokines including IL-6. In view of the large amounts of de novo synthesis induced by the activation of rat peritoneal mast cells and previous observations of expression of this cytokine by human lung mast cells, we have studied the regulation of IL-6 production. We examined the hypothesis that mast cell IL-6 production is not related to previous histamine release. Highly purified rat peritoneal mast cells were activated with anti-IgE, calcium ionophore A23187, or LPS. Histamine was used as a marker of preformed mediator release and IL-6 production was assessed by using the B9 hybridoma growth factor bioassay. Anti-IgE activation of rat peritoneal mast cells induced IL-6 production and histamine release. In contrast, LPS activation induced substantial, serum-dependent, IL-6 production without a significant level of histamine release. No preformed IL-6 was detected in the cells. Calcium ionophore induced histamine release from mast cells to a greater extent than did anti-IgE, but no A23187-induced IL-6 production was observed. A23187-treated cells retained high viability and produced a significant amount of TNF-alpha. To further examine the concordance of IL-6 production and histamine release we used mast cell stabilizing drugs. Dexamethasone and nedocromil significantly inhibited IL-6 production in response to anti-IgE. Our results demonstrate that there is not a direct relationship between mast cell degranulation and IL-6 production. Our observations are important for understanding the role of mast cells in inflammation and for developing strategies to modulate mast cell function in disease.
 ...
PMID:IL-6 production by rat peritoneal mast cells is not necessarily preceded by histamine release and can be induced by bacterial lipopolysaccharide. 751 39


1 2 3 4 5 6 7 Next >>