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)

This study characterised the effect of beta-adrenoceptor stimulation on endotoxin-induced accumulation of neutrophilic granulocytes in mouse airways, where the cytokines interleukin (IL)-6 and macrophage inflammatory protein (MIP)-2 are involed as mediators. The beta2-adrenoceptor agonist salbutamol (0.025-250 fMol) was administered intranasally in mice 24 h prior to administration of endotoxin (10 microg) intranasally. Bronchoalveolar lavage (BAL) fluid and venous blood, respectively, was harvested (6 or 24 h) after administration of endotoxin. Salbutamol substantially decreased the number of neutrophils in BAL fluid from endotoxin-exposed (6 and 24 h) mice and this effect was dose dependent (24 h). Pretreatment with the beta-adrenoceptor antagonist propranolol attenuated the inhibitory effect of salbutamol on BAL neutrophils (6 and 24 h), an attenuation that was not due to any unspecific effect of propranolol. Salbutamol also substantially decreased IL-6, but not MIP-2 in BAL fluid (6 h). In contrast to BAL fluid, salbutamol caused a moderate increase in blood neutrophils (24 h). In conclusion, as indicated in mouse airways in vivo, beta-adrenoceptor stimulation prior to endotoxin exposure inhibits the induced accumulation of neutrophils at a time point much later than that anticipated from its bronchodilatory effect. Even though the detailed molecular mechanisms behind this sustained "anti-inflammatory" effect remain unknown, it seems likely that this effect is in part due to a decrease in the local concentration of interleukin-6.
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PMID:Beta-adrenoceptor stimulation and neutrophil accumulation in mouse airways. 1533 90

The combination of beta(2)-adrenoceptor agonists (beta(2)-agonists) with inhaled steroids has become the standard treatment for mild to moderate asthma. Theophylline has also been combined successfully with inhaled steroids. However, the possible interaction between theophylline and beta(2)-agonists, with regard to their anti-inflammatory effects, has not been clarified. The aim of this study was to investigate the in vitro interaction between theophylline and salbutamol on cytokine generation from human monocytes and compare it with a similar interaction between dexamethasone and salbutamol. Purified monocytes from normal donors were pretreated with the drugs (alone or in combination) and stimulated with lipopolysaccharide for 24 h. Released tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), and their corresponding mRNA expressions, were determined and analyzed. Salbutamol (>or= 0.1 microM) significantly inhibited the release of TNF-alpha, but also significantly enhanced that of IL-6. In contrast, theophylline (50 microM) and dexamethasone (0.1 microM) strongly inhibited the generation of both cytokines. It is noteworthy that when the drugs were used in combination the effects of theophylline and salbutamol were additive in inhibiting TNF-alpha release, but theophylline blocked the IL-6-enhancing effect of salbutamol. A similar effect was seen when dexamethasone was combined with salbutamol. These results show that beta(2)-agonists have opposing effects on the generation of TNF-alpha and IL-6, but that when they were combined with clinically relevant concentrations of theophylline, theophylline, like dexamethasone, was capable of augmenting the anti-inflammatory effects of the beta(2)-agonists while at the same time preventing their proinflammatory effect. Thus, theophylline may have a potentially useful steroid-sparing effect.
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PMID:Interactions between theophylline and salbutamol on cytokine release in human monocytes. 2038 27