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)

Down-regulation of cytokine production in activated human blood monocytes (BMs) and alveolar macrophages (AMs) can be achieved in vitro by treatment with corticosteroids. The inhibition of cytokine secretion by corticosteroids may have important therapeutic consequences in e.g. asthma. However, relatively little is known about possible differences in the sensitivity of different cytokines to corticosteroid treatment. Homologous BMs and AMs were obtained from six healthy volunteers. Secretion of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the cultures of lipopolysaccharide (LPS) stimulated adherent BMs and AMs was analysed using specific immunoassays. Sensitivity of the IL-1 beta, IL-6, and GM-CSF secretion to the in vitro treatment with a synthetic corticosteroid, budesonide, was compared. BMs and AMs displayed significant differences in both cytokine secretion and susceptibility to regulation by budesonide. When added to the BM cultures concomitantly with LPS, budesonide suppressed IL-1 beta and IL-6 only partially (to 30% of the control level). In contrast, GM-CSF release in these cultures was almost totally inhibited by budesonide (> or = 10(-8) M). The IC50 for inhibition of the GM-CSF secretion was as low as 2 x 10(-10) M. In the AM cultures, budesonide had very little effect on IL-1 beta and IL-6 secretion (inhibition to 80% and 60% of control levels, respectively), while GM-CSF secretion was suppressed to 20% of control by budesonide concentrations > or = 10(-7) M.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of a corticosteroid, budesonide, on alveolar macrophage and blood monocyte secretion of cytokines: differential sensitivity of GM-CSF, IL-1 beta, and IL-6. 800 51

Eighteen children with perennial asthma and allergy to house-dust mite (HDM) underwent a bronchial challenge with HDM. Before and 24 h after the test, a venous blood sample was taken to determine levels of eosinophils, eosinophil cationic protein (ECP), soluble interleukin-2 receptor (IL-2R), and interleukin-6 (IL-6). A histamine challenge was performed before and 24 h after the HDM challenge. All subjects showed an immediate asthmatic reaction (IAR). A definite late asthmatic reaction (LAR) was observed in 15 children, a probable LAR in two, and no LAR in one. Because of persistent bronchial obstruction (FEV1 < 70%), eight children were unable to perform a histamine challenge 24 h after the allergen challenge. These were the children with the lowest prechallenge provocation dose (PD20) of histamine. In the other 10 children, the mean PD20 histamine decreased after the HDM challenge (mean PD20 before was 0.56 mg/ml; after challenge it was 0.14 mg/ml; P = 0.007). After the HDM challenge, an increase was detected in the mean values of blood eosinophils (mean before was 446/mm3; mean after was 733/mm3; P = 0.002), ECP (mean before was 26.3 micrograms/l; mean after was 34.3 micrograms/l; P < 0.040), and IL-2R (mean before was 116.35 U/ml; mean after was 128.52 U/ml; P < 0.040). On the other hand, IL-6 remained unchanged after the HDM challenge (mean before was 9.47 pg/l; mean after was 9.70 pg/l; P = 0.360).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of a bronchial provocation test with house-dust mite on blood eosinophilia, eosinophil cationic protein, soluble interleukin-2 receptor, and interleukin-6 in asthmatic children. 823

Myofibroblasts have been previously described beneath the bronchial epithelium and were found to increase in number proportional to the accumulation of extracellular matrix in the bronchial lamina reticularis in asthma. The aim of this study was to assess further the contribution of these structural cells to allergic inflammation in the bronchial mucosa through their cytokine expression. Cell cultures were established from the lamina reticularis of human bronchial biopsies from asthmatic and non-asthmatic subjects. Cytokine secretion was measured by ELISA in supernatants of cultures with or without tumour necrosis factor-alpha (TNF-alpha). The mRNA levels for granulocyte-macrophage colony-stimulating factor (GM-CSF) in the cultures were examined by ribonuclease protection assays (RPAs). Bronchial myofibroblasts grown from bronchial biopsies were capable of producing GM-CSF, interleukin-6 (IL-6), interleukin-8 (IL-8), and stem cell factor (SCF) constitutively. The GM-CSF production by myofibroblasts was significantly increased in response to TNF-alpha simulation with a corresponding increase in GM-CSF mRNA expression. The enhancement of GM-CSF production by TNF-alpha in myofibroblasts was blocked by the inhibition of RNA synthesis. Prednisolone abolished the GM-CSF production. This study provides evidence for the role of bronchial myofibroblasts in the regulation of inflammatory cell recruitment and activation by interaction in the cytokine network in the bronchial mucosa.
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PMID:Cytokine production by cell cultures from bronchial subepithelial myofibroblasts. 894 23

In allergic asthma, inhalation of antigen provokes an early increase in microvascular permeability with protein extravasation and a delayed recruitment of inflammatory cells. We showed that similar concentrations of lipopolysaccharide (LPS) are present in bronchoalveolar lavage fluid (BALF) in 12 subjects without asthma (86.5 +/- 53.8 pg/ml) and 12 subjects with mild asthma (111 +/- 37.0 pg/ml). These LPS levels are insufficient to stimulate cytokine release without accessory molecules. BALF obtained 24 h after segmental ragweed antigen challenge in 11 asthmatics allergic to ragweed contained increased levels of two LPS accessory molecules compared with preantigen BALF, 158-fold more LPS-binding protein (LBP) 4.83 +/- 2.02 vs. 742 +/- 387 ng/ml; P < 0.03) and 31.6-fold more soluble CD14 (sCD14) (3.45 +/- 1.04 vs. 110 +/- 51.6 ng/ml; P < 0.02). Postantigen BALF enhanced binding of fluorescein-conjugated LPS to CD14-bearing THP-1 cells and supported LPS-induced non-CD14-bearing endothelial cell expression of intercellular adhesion molecule-1 and interleukin-6, indicating functional LBP and sCD14. We suggest that extravasation of LBP and sCD14 into the bronchoalveolar compartment after antigen inhalation may enhance the capacity of inhaled or aspirated LPS to activate an inflammatory cascade that may amplify the inflammatory response to inhaled antigen in some asthmatics.
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PMID:Asthma and endotoxin: lipopolysaccharide-binding protein and soluble CD14 in bronchoalveolar compartment. 896 7

The binding of immunoglobulin E (IgE) to high affinity IgE receptors (Fc(epsilon)RI) expressed on the surface of mast cells primes these cells to secrete, upon subsequent exposure to specific antigen, a panel of proinflammatory mediators, which includes cytokines that can also have immunoregulatory activities. This IgE- and antigen-specific mast cell activation and mediator production is thought to be critical to the pathogenesis of allergic disorders, such as anaphylaxis and asthma, and also contributes to host defense against parasites. We now report that exposure to IgE results in a striking (up to 32-fold) upregulation of surface expression of Fc(epsilon)RI on mouse mast cells in vitro or in vivo. Moreover, baseline levels of Fc(epsilon)RI expression on peritoneal mast cells from genetically IgE-deficient (IgE -/-) mice are dramatically reduced (by approximately 83%) compared with those on cells from the corresponding normal mice. In vitro studies indicate that the IgE-dependent upregulation of mouse mast cell Fc(epsilon)RI expression has two components: an early cycloheximide-insensitive phase, followed by a later and more sustained component that is highly sensitive to inhibition by cycloheximide. In turn, IgE-dependent upregulation of Fc(epsilon)RI expression significantly enhances the ability of mouse mast cells to release serotonin, interleukin-6 (IL-6), and IL-4 in response to challenge with IgE and specific antigen. The demonstration that IgE-dependent enhancement of mast cell Fc(epsilon)RI expression permits mast cells to respond to antigen challenge with increased production of proinflammatory and immunoregulatory mediators provides new insights into both the pathogenesis of allergic diseases and the regulation of protective host responses to parasites.
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PMID:IgE enhances mouse mast cell Fc(epsilon)RI expression in vitro and in vivo: evidence for a novel amplification mechanism in IgE-dependent reactions. 903 45

Studies were undertaken to determine whether differences in serum cytokine balances could be involved in the pathogenesis of allergic and in non-allergic asthma. At this propose, interferon-gamma, tumor necrosis factor-alpha, interleukin-2, interleukin-4, interleukin-6, and interleukin-10 were measured by enzimoimmunoassay. The analysis was performed on 24 allergic and 24 non-allergic asthmatic patients and 16 healthy subjects. IFN-gamma and TNF-alpha, included into the type 1 cytokines, appeared significantly increased in the allergic with respect to the non-allergic asthmatic patients (p = 0.01) and (p < 0.001) respectively, while IL-10, which belongs to the type 2 cytokines, was significantly increased in the non-allergic asthmatic (p < 0.001). The IL-6 analysis did not show any significant difference in either of the study group. The most interesting finding was the high serum IL-10 values detected in intrinsic asthmatic patients, which in turn, suggests that this cytokine could participate in the regulation of different immunological features that occurs in non-allergic asthma, and maybe it could indicate a higher stimulated state of cells in this type of asthma. The data presented in this report show a different cytokine profile in serum from allergic and non-allergic asthmatic patients and denote a stronger prevalence of type 2 cytokines in intrinsic asthma.
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PMID:Cytokine serum profiles in allergic and non-allergic asthma. Increased production of IL-10 by non-allergic asthmatic patients. 915 Aug 41

Asthma is an inflammatory airway disorder, traditionally subdivided into extrinsic, immunoglobulin E (IgE)-mediated, and intrinsic asthma of unknown aetiology. IgE synthesis requires contact between T- and B-cells and a signal provided by interleukin (IL)-4, which can be modulated by IL-6. The objective of this study was to evaluate the effects of IL-4 and IL-6 on total IgE synthesis by peripheral blood mononuclear cells from intrinsic and extrinsic asthmatics. Peripheral blood mononuclear cells from intrinsic and extrinsic asthmatic patients and from healthy subjects were cultured and stimulated with pokeweed mitogen, recombinant IL-4 and IL-6. The IgE level in serum and supernatants was measured by an enzyme-linked immunoassay. Serum IgE was significantly lower in intrinsic asthma than in extrinsic asthma, but significantly higher than in control subjects. IgE production by cultured mononuclear cells from extrinsic asthmatics was not modified after exogenous IL-4 and IL-6 addition. However, intrinsic asthmatics showed enhancement of IgE synthesis in response to IL-4 stimulation, reaching a threefold increase of the spontaneous IgE values, when simultaneous recombinant IL-4 plus IL-6 stimulus was used. Our results indicate that exogenous recombinant interleukin-6 can significantly upregulate the interleukin-4-dependent immunoglobulin E synthesis in intrinsic asthma. This suggests that immunoglobulin E could also play a role in the pathogenesis of intrinsic asthma, in which an interleukin-6 threshold would be critical.
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PMID:Co-stimulation of cultured peripheral blood mononuclear cells from intrinsic asthmatics with exogenous recombinant IL-6 produce high levels of IL-4-dependent IgE. 931 9

In the search for markers of airway inflammation, we investigated the role of soluble interleukin-6 receptor (sIL-6R) in patients with bronchial asthma. Serum levels of sIL-6R were measured in 20 patients with stable asthma and in 18 healthy control subjects by means of a sandwich enzyme-linked immunosorbent assay. Such levels were also evaluated during a spontaneous attack of asthma (n = 10) as well as that after allergen inhalation (n = 7). Results were compared with those observed during the stable state and after the inhalation of methacholine. Serum levels of sIL-6R in asthmatic patients (132 +/- 31 ng/ml) significantly exceeded those of control subjects (111 +/- 16 ng/ml) (p < 0.05). These levels showed no correlation with such clinical variables as nonspecific bronchial hyperreactivity, atopic status, or serum concentration of IgE. Serum sIL-6R levels observed during an asthmatic attack versus those during the stable state (4 wk later) differed significantly. After a severe attack of asthma, such levels were significantly elevated on the second and third days, but not on Day 5. After challenge, circulating levels of sIL-6R were significantly increased 24 h after the inhalation of allergen but not of methacholine. Results suggest that serum levels of sIL-6R are increased in patients with asthma and are further increased during a spontaneous attack or that provoked by the inhalation of allergen. Thus, serum sIL-6R may reflect inflammation of the airway. Further studies are indicated to determine the clinical significance and the application of serum levels of sIL-6R in evaluating asthmatic patients.
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PMID:Circulating levels of soluble interleukin-6 receptor in patients with bronchial asthma. 937 94

Toluene diisocyanate (TDI) can cause occupational asthma, but the mechanism underlying sensitization to this chemical compound remains controversial. The present study aims to investigate whether tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) liberated in the lungs after TDI inhalation can contribute to the migration of dendritic cells from respiratory airways towards lung associated lymph nodes for presentation of TDI hapten. Exposure was studied in two modes: (1) acute exposure (experiment no. 1, 2 and 3) where animals were exposed to 2.962, 1.060, and 1.076 ppm TDI for 1, 4, and two periods of 4 h, respectively; (2) subacute exposure (experiment no. 4, 5 and 6) where animals were exposed to 0.066, 0.110, and 0.999 ppm TDI for 48 h for the two lower doses and 5 days for the highest dose. Depending on the modes of exposure, two to four post exposure times were selected. After acute exposure to 2.962 ppm TDI for 1 h, the increase in TNF-alpha and IL-6 levels in bronchoalveolar lavage (BAL) fluid was observed immediately at the end of inhalation exposure, whereas the maximum number of dendritic cells and total cells occurred at post exposure times of 48 h and 5 days, respectively. In two other acute exposures, the peak increases in TNF-alpha, IL-6 and total cell numbers were observed at 48 h post exposure time, whereas the peak increase in dendritic cells occurred at 24 h. After subacute exposure to 48 h TDI, where TDI concentrations were relatively low (0.006 or 0.110 ppm), a parallel increase in TNF-alpha and IL-6 levels, dendritic and total cell numbers were observed at 0 h post exposure time. This phenomenon was also apparent at 24 h post exposure time when the animals had been exposed to 1.999 ppm TDI for 5 days. From these results, we can conclude that dendritic cells could play a key role as antigen presenting cells in the development of TDI-induced respiratory sensitization, and that their migration toward lung-associated lymph nodes is probably conditioned by cytokine release in their micro-environment. Future work must delineate whether TNF-alpha and IL-6 are solely responsible for the migration of dendritic cells after TDI inhalation, for example by using antibodies to neutralize these cytokines.
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PMID:TDI inhalation in guinea-pigs involves migration of dendritic cells. 948 55

Antiasthma drugs are now being re-evaluated for their anti-inflammatory effects. Theophylline is an immunomodulator; however, weak effects and the narrow therapeutic window make it a controversial drug. We compared the immunomodulatory potencies of theophylline with those of the xanthines pentoxifylline (POF) and A802715. Using a whole-blood, cell-culture system, we studied the effects on the release of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin-6 (IL-6) in six healthy subjects, and, in granulocyte suspensions, the effects on the release of reactive oxygen species (ROS). We also studied the influence of a 14-day treatment with theophylline or POF on the release of the cytokines named above in 14 asthmatics. We found that equimolar concentrations of A802715 most effectively inhibit ROS generation, followed by POF; the effects of theophylline were weakest. A802715-inhibited release of TNF-alpha was four times as potent as that of theophylline, and POF two times as potent. Inhibition of IFN-gamma by A802715 was three times as potent, and by POF two times. Neither drug influenced IL-6 release. After a 14-day treatment of asthmatics, POF proved to inhibit TNF-alpha release more effectively (by 44.3%) than theophylline (7.5%). It is concluded that study of xanthine derivatives in asthmatics might help the development of asthma therapy. POF seems to be an especially promising candidate.
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PMID:Differences in the anti-inflammatory effects of theophylline and pentoxifylline: important for the development of asthma therapy? 972 23


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