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V Lagente

Publications and source records attributed to V Lagente.

At least 55 records · Page 3Linked to original sources
PubMed1997

Selective type IV phosphodiesterase inhibitors prevent IL-4-induced IgE production by human peripheral blood mononuclear cells.

BACKGROUND: Selective type IV phosphodiesterase (PDE) inhibitors elicit anti-inflammatory and bronchodilatory activities in vitro and in vivo which suggest that these drugs could provide a new therapeutic approach for asthma treatment. OBJECTIVE: Regarding the role of IgE production in allergic and inflammatory reactions of the airways, we investigated the effect of selective PDE inhibitors on IL-4-driven IgE production by peripheral blood mononuclear cells (PBMC) or by purified B lymphocytes. METHODS: PBMC or purified B lymphocytes from non-allergic donors were stimulated for 13 days with IL-4 (100 U/mL) in the presence or in the absence of selective PDE inhibitors. IgE production is evaluated by an ELISA technique. RESULTS: The selective PDE IV inhibitors, rolipram and Ro 20-1724 (10 microM), inhibit IL-4-induced IgE production by PBMC, but not by purified B lymphocytes. No modification of the IgE production was noted with the selective PDE III inhibitors, milrinone and SK&F 94-836, or the selective PDE V inhibitor, SK&F 96-231 (10 microM). Flow cytometry experiments showed that the effect of Rolipram could not be explained by the inhibition of the cell surface expression of the IL-4 receptor. Similarly, no significant effect of PDE IV inhibitors was observed on PHA-induced cell proliferation. The incubation of monocytes only with rolipram was sufficient to achieve a significant reduction of IgE production induced by IL-4. CONCLUSION: Taken together, these results indicate that PDE IV inhibitors reduce IL-4-induced IgE production by PBMC and suggest that the inhibition of IgE production could be explained by a failure of monocytes to provide the necessary costimulatory signals.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed1996

Selective inhibition of phosphodiesterase type IV suppresses the chemotactic responsiveness of rat eosinophils in vitro.

Previous studies demonstrated that the selective inhibition of phosphodiesterase type IV suppresses antigen-induced eosinophil infiltration and also downregulates certain eosinophil functions assessed in vitro. In the current study, we compared the effect of selective inhibitors of phosphodiesterase IV with the effect of phosphodiesterase III and V inhibitors, focusing on eosinophil chemotaxis stimulated by platelet-activating factor (PAF) and leukotriene B4 in a modified Boyden chamber. The effect of beta 2-adrenoceptor agonists and forskolin as well as the analogue N6-2'-O-dibutyryladenosine 3':5'-cyclic monophosphate (Bt2 cyclic AMP) was also determined. For this purpose eosinophils were obtained by lavage of the peritoneal cavity of normal Wistar rats and purified on Percoll gradients to 85-95% purity. Our results showed that PAF and leukotriene B4 (0.001-10 microM) elicited a concentration-dependent increase in eosinophil migration with maximal responses observed at 1 microM and 0.1 microM respectively. Pre-incubation with the type IV phosphodiesterase inhibitor, rolipram (1-100 microM), suppressed the chemotactic response triggered by PAF and leukotriene B4, in association with elevation of eosinophil cyclic AMP, whereas the compounds milrinone and SK&F 94836 (type III selective) as well as zaprinast (type V selective) were ineffective. The beta 2-adrenoceptor agonists salbutamol and salmeterol (1-100 microM) did not alter the intracellular levels of cyclic AMP and also failed to inhibit the eosinophil response. Moreover, incubation of eosinophils with the adenylate cyclase activator forskolin (1-100 microM), while inducing a discrete increase in cyclic AMP, markedly inhibited PAF- and leukotriene B4-induced eosinophil chemotaxis. Eosinophils treated with a combination of individually inactive amounts of forskolin plus rolipram significantly inhibited the eosinophil migration elicited by PAF and leukotriene B4, but did not change cyclic AMP baseline levels. Though only at the highest concentration tested (100 microM), the analogue Bt2 cyclic AMP abolished the eosinophil chemotaxis. Thus we conclude that the direct inhibitory effect of phosphodiesterase IV inhibitors on eosinophil chemotaxis may account for their suppressive activity on tissue eosinophil accumulation following antigen challenge.

Adrenergic beta-Agonists↗
PubMed1996

Differential inhibition by selective phosphodiesterase inhibitors of antigen, LTC4 and histamine-induced contraction of guinea-pig isolated trachea.

Antigen (ovalbumin)-induced contraction of guinea-pig isolated trachea, which largely resulted from the endogenous release of peptidoleukotrienes, was strongly inhibited by the non-selective phosphodiesterase (PDE) inhibitor theophylline and, more potently, by the selective PDE type IV inhibitors rolipram and Ro 20-1724. It was also strongly inhibited by the PDE type V inhibitor zaprinast, but much less so by the PDE type III inhibitor siguazodan and milrinone. Similar results were obtained in trachea minus epithelium. In contrast to their effects vs. allergic airway smooth muscle contraction, both milrinone and siguazodan potently relaxed leukotriene C4 (LTC4)-induced contraction in isolated trachea from non-sensitized animals. In this assay, rolipram, Ro 20-1724 and zaprinast were less active compared to their effects vs. ovalbumin-induced contraction, whereas theophylline had equivalent potency in the two tests. The relative potencies of rolipram and siguazodan in relaxation of trachea were similar when added prior to or after either LTC4 or histamine. These results suggest that the higher potency of selective PDE type IV & V inhibitors compared with PDE type III inhibitors vs. ovalbumin-induced contraction is due to their greater inhibition of anaphylactic mediator release. The converse is true if we consider their bronchodilator actions, although the superior efficacy of selective PDE type III inhibitors over PDE type IV inhibitors may vary in sensitized vs. non-sensitized animals. The present results are in agreement with a previous study showing that low concentrations of a beta 2-agonist increased the relaxant effect of selective PDE type IV inhibitors in guinea-pig trachea. The present data indicate that prophylactic use of selective PDE type IV inhibitors combined with therapeutic use of low dose inhaled beta-agonist might represent an alternative to the use of antiallergic or steroid therapy in asthma.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed1996

Interactions between cAMP- and cGMP-dependent protein kinase inhibitors and phosphodiesterase IV inhibitors on arachidonate release from human monocytes.

The effects of specific inhibitors of cAMP-dependent protein kinase (PKA) and cGMP-dependent protein kinase (PKG) on the inhibitory activity of phosphodiesterase (PDE) type IV inhibitors and of the cell permeable analogue of cAMP, db-cAMP, were investigated on fMLP-induced arachidonate release from human monocytes. When monocytes were preincubated with the combined PKA/PKG inhibitor H8 (10(-6) to 10(-4) M) or the selective PKG inhibitor Rp-8-cpt-cGMPs (10(-6) to 10(-4) M) a concentration-dependent reduction of the inhibitory effect of db-cAMP (10(-3) M), rolipram (10(-5) M) and Ro 20-1724 (10(-5) M) was noted. When monocytes were preincubated with the selective PKA inhibitor H89 (10(-6) to 10(-4) M), only a small inhibition of the effect of db-cAMP and no inhibition of the effects of rolipram and Ro 20-1724 were observed. The present data indicate that db-cAMP and PDE IV inhibitors elicit an in vitro anti-inflammatory activity by a PKA-independent mechanism, which do not appear to be mainly mediated via the PKG activation.

Arachidonic Acid↗
PubMed1996

Salbutamol potentiates the relaxant effects of selective phosphodiesterase inhibitors on guinea pig isolated trachea.

The ability of low concentrations of salbutamol to potentiate the relaxant effects of the phosphodiesterase (PDE) inhibitors, rolipram, Ro 20-1724 (PDE type IV inhibitor), siguazodan and milrinone (PDE type III inhibitor) was studied on guinea pig isolated trachea. These PDE inhibitors were strong relaxants of guinea pig trachealis under basal tone, but had only a weak activity on tissues precontracted with histamine (10(-5) M). In both cases, PDE type IV inhibitors showed a relaxant effect composed of two phases. The first phase represented 20 and 40% and the second, 90 and 140%, respectively, of relaxation of basal tone and histamine-induced tone. A second characteristic of PDE type IV inhibitors was the very fast and partially reversible relaxation observed at concentrations greater than 3 x 10(-8) M (for histamine-induced tone) at the first addition of inhibitor, followed by a residual relaxant activity. The latter relaxant effect was stable at concentrations of 3 x 10(-8)-10(-5) M and was equivalent to a 20% relaxation (for histamine-induced tone). In the presence of low concentrations (10(-9) and 10(-8) M) of salbutamol, there was a significant concentration-dependent potentiation of the effects of PDE inhibitors on trachea precontracted with histamine. Salbutamol, at a concentration of 10(-9) M, potentiated the effects of PDE inhibitors between 1.4- and 3.6-fold. In the presence of salbutamol 10(-8) M, the potentiation was more marked for siguazodan (37.9-fold), milrinone (11.0-fold) and Ro 20-1724 (14.5-fold) than for rolipram (4.3-fold). These results suggest that low concentrations of salbutamol can potentiate the relaxant effects of both PDE type III and PDE type IV inhibitors. Thus, PDE type IV inhibitors, which have antiinflammatory properties, could also provide adequate bronchodilation when used in combination with lower than usual doses of beta 2-agonists.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed1996

Role of cyclic AMP in the modulation of IgE production by the beta 2-adrenoceptor agonist, fenoterol.

We have previously demonstrated that the beta 2-adrenoceptor agonist, salbutamol, potentiates the effect of interleukin-4 (IL-4) on immunoglobulin E (IgE) production by human peripheral blood mononuclear cells (PBMC). This study was undertaken to further define the activities of these drugs and the role of cyclic-adenosine monophosphate (cAMP) in the modulation of IgE production. Our results indicate that fenoterol (1 microM) potentiated IL-4-induced IgE production and IgE messenger ribonucleic acid (mRNA) expression. Moreover, this effect was associated with an increase in intracellular cAMP levels. The activities of this drug on IgE production were mimicked by cell permeable cAMP analogues, such as dibutyryl-cAMP (db-cAMP) (100 microM) or Sp-AMP (10 microM). The potentiating effect of fenoterol on IgE production was markedly inhibited in the presence of protein kinase A (PKA) inhibitors: H8 (10 microM) and Rp-AMP (10 microM), suggesting that its effects are likely to depend on the activation of the cAMP pathway. Additionally, the potentiating effect of fenoterol was also blocked in the presence of indomethacin. Fenoterol potentiated IL-4-induced IgE production from purified B-cells activated through their CD40 antigen. This effect was associated with an increase in cellular viability. Therefore, the activities of this drug on PBMC are likely to be mediated by the activation of another cellular type. Taken together, these results show that fenoterol potentiates the IL-4-induced IgE production via the cAMP pathway, but that this enhancement could not be explained by a direct effect on B-lymphocytes.

Adrenergic beta-Agonists↗
PubMed1996

Involvement of tachykinin NK1 and NK2 receptors in substance P-induced microvascular leakage hypersensitivity and airway hyperresponsiveness in guinea-pigs.

Tachykinins, such as substance P, might be involved in the development of airway hyperresponsiveness (AHR) and airway inflammation. However, it is unknown which tachykinin receptors mediate these biological activities. The effects of two antagonists of tachykinin neurokinin-1 (NK1) and tachykinin neurokinin-2 (NK2) receptors, SR 140333 and SR 48968, respectively, were investigated on substance P (SP)-induced airway hyperresponsiveness and potentiation of the histamine-induced increase in microvascular leakage, in phosphoramidon-pretreated guinea-pigs. Guinea-pigs were pretreated with phosphoramidon (0.1 mM aerosol for 15 min) and exposed 15 min later to saline solution alone or to saline solution containing SP (0.1 mg.mL-1 for 30 min). Twenty four hours later, the animals were anaesthetized and prepared for the recording of the pulmonary inflation pressure (PIP) to acetylcholine or for the investigation of microvascular leakage to histamine. Pretreatment of the guinea-pigs with a single dose of SR 48968 (1 mg.kg-1, i.p.) 30 min before SP exposure, significantly prevented the development of AHR, whereas SR 140333 (1 mg.kg-1, i.p.) did not. In a second set of experiments, phosphoramidon-pretreated guinea-pigs exposed to SP presented a significant potentiation of the histamine-induced increase in microvascular leakage in pulmonary airways. When the guinea-pigs were pretreated with SR 140333, an inhibition of the increased microvascular leakage to histamine was observed. In contrast, no significant inhibitory activity was noted when the guinea-pigs were pretreated with SR 48968. The present data demonstrate the importance of tachykinin NK2 receptor stimulation in the development of airway hyperresponsiveness and that of tachykinin NK1 receptor stimulation in microvascular leakage hypersensitivity in phosphoramidon-pretreated and substance P-exposed guinea-pigs. The results also suggest a dissociation between the presence of microvascular leakage and the occurrence of airway hyperresponsiveness.

Animals↗
PubMed1995

Involvement of cyclic AMP in the effects of phosphodiesterase IV inhibitors on arachidonate release from mononuclear cells.

The effects of selective phosphodiesterase inhibitors, cyclic AMP (cAMP) elevating agents and stable analogues of cyclic nucleotides, on the release of arachidonate induced by N-formyl-Met-Leu-Phe (fMLP) were investigated on human peripheral blood mononuclear cells. The selective phosphodiesterase IV inhibitors, rolipram and Ro 20-1724, and the non-selective phosphodiesterase inhibitor, theophylline, elicited a concentration-dependent inhibition of arachidonate release (EC50 = 1.3 x 10(-6) M, 3.2 x 10(-6) M and 3.7 x 10(-4) M respectively). The selective phosphodiesterase III inhibitor, milrinone (10(-5) M), only caused a slight effect while the phosphodiesterase V inhibitor, zaprinast (10(-5) M), the beta 2-adrenoceptor agonists, salbutamol and fenoterol (10(-5) M), failed to inhibit arachidonate release. Forskolin (10(-5) M) and N6,2'-O- dibutyryladenosine 3':5'-cyclic monophosphate (db-cAMP), 10(-3) M) elicited a moderate inhibition. Forskolin increased the effects of rolipram and Ro 20-1724 (EC50 = 4.5 10(-7) M and 4 x 10(-7) M respectively). Incubation of the cells with rolipram (10(-8) to 10(-5) M), Ro 20-1724 (10(-8) to 10(-5) M, forskolin (10(-5) M) or salbutamol (10(-5) M) alone, induced a moderate increase or no increase at all in intracellular cAMP. However, in the presence of forskolin, rolipram (10(-8) to 10(-6) M) and Ro 20-1724 (10(-8) to 10(-6) M) induced significant and concentration-dependent increase in intracellular levels of cAMP. These results suggest that the potent inhibition of arachidonate release from mononuclear cells by selective phosphodiesterase IV inhibitors may be due to increases in discrete pools of intracellular cAMP.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed1995

Role of PAF in the late airway microvascular leakage induced by antigen in IgE-sensitized rat.

The effect of the antagonist of platelet-activating factor (PAF), BN 50730, on PAF-and antigen- induced increase in microvascular leakage, using Evans blue dye as an index of permeability, was investigated in rat pulmonary tissues. PAF (1 microgram/kg, iv) induced a marked increase in Evans blue dye content in trachea, main bronchi and small bronchi, that was significantly reduced upon pretreatment of the rats with BN 50730 (25 mg/kg, orally) and by the serotonin antagonist, methysergide (1 mg/kg, iv), only in the small bronchi. Serotonin also induced an increase in microvascular leakage in the three tissues that was significantly inhibited when the animals were treated with methysergide but not by BN 50730. In contrast, histamine and lyso-PAF did not induce significant increase in Evans blue dye content. Intravenous injection of antigen to IgE-sensitized rats induced a biphasic increase in vascular permeability. An early increase in vascular permeability in trachea, main bronchi and small bronchi was observed 10 minutes after the injection of the antigen, and this phenomenon was significantly reduced upon treatment of the rats with methysergide, whereas, BN 50730 was ineffective. A late increase in vascular permeability was noted in the three tissues, with a maximum at 120 minutes and representing 30-40% of the magnitude of the first phase. Administration of BN 50730 (25 mg/kg) to the animals, evoked a significant inhibition of this increase in microvascular leakage, whereas, methysergide only significantly reduced the one induced by antigen in the trachea.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

Prevention by the tachykinin NK2 receptor antagonist, SR 48968, of antigen-induced airway hyperresponsiveness in sensitized guinea-pigs.

The involvement of tachykinins in antigen-induced airway hyperresponsiveness (AHR) was characterized pharmacologically in guinea-pigs sensitized to ovalbumin with antagonists of tachykinin NK1 and NK2 receptors, namely SR 140333 and SR 48968, respectively. AHR was illustrated by increased sensitivity to bronchoconstriction provoked by aerosolized acetylcholine in anaesthetized, ventilated animals, administrated 48 h after ovalbumin aerosol challenge. SR 48968 (1 mg kg-1, i.p.), when given once 30 min before the antigen challenge, prevented AHR, whereas SR 140333 did not. These findings suggest that the tachykinin NK2 receptor antagonist, SR 48968, may be useful for investigating mechanisms of tachykinins in the development of airway hyperresponsiveness.

Acetylcholine↗
PubMed1995

Modulation of cytokine-induced eosinophil infiltration by phosphodiesterase inhibitors.

The effects of selective phosphodiesterase (PDE) isoenzyme inhibitors on eosinophil airway infiltration induced by intratracheal administration of recombinant human cytokines were investigated in the guinea pig. Recombinant human IL-5 and IL-8 elicited a concentration-dependent increase in the number of eosinophils in the bronchoalveolar lavage (BAL) fluid. In contrast, no effect was observed after intratracheal injection of recombinant human IL-3 or recombinant human RANTES. Pretreatment with the PDE IV inhibitors rolipram or Ro 20-1724 or the nonselective PDE inhibitor theophylline 1 h before intratracheal injection of IL-5 significantly reduced the number of eosinophils in the BAL fluid at 48 h. In contrast, the selective PDE III inhibitors milrinone and SK&F 94-836 and the PDE I/V inhibitor zaprinast did not inhibit the airway eosinophil infiltration induced by IL-5. Betamethasone also significantly inhibited the IL-5-induced eosinophil infiltration in BAL fluid. Administration of rolipram or betamethasone 1 h before IL-8 significantly reduced airway eosinophil infiltration. Because the selective PDE IV inhibitors markedly inhibited eosinophil infiltration in guinea pig airways induced by cytokines, it is suggested that PDE IV inhibitors have antiinflammatory effects in the airways and may be useful in the treatment of asthma.

Animals↗
PubMed1995

Asthma and airway inflammation: potential anti-inflammatory activities of phosphodiesterase inhibitors.

Asthma is now recognized as an inflammatory disease associated with eosinophil infiltration into the pulmonary tissue. It has appeared in recent years that phosphodiesterase type IV inhibitors presented all the necessary characteristics to be used as new anti-asthmatic drugs. Indeed, in addition to their bronchodilator properties, they have inhibitory activities on inflammatory cell infiltration into the lung and on inflammatory mediator release. However, the mechanism of action of phosphodiesterase inhibitors, theoretically linked to the increase in intracellular cAMP, is now largely open for discussion.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1995

[Effects of beta-adrenergic compounds on IgE production].

We studied the effects of beta 2-adrenoceptor agonist on IgE production in vitro in human and in vitro and in vivo in mouse. We observed that salbutamol and fenoterol potentiate the IL-4-induced IgE production from peripheral blood mononuclear cells. This effect is associated by an enhanced mRN expression for IgE. Fenoterol also potentiated, but in a lesser extent, the IgE production from purified B lymphocytes stimulated by both IL-4 and CD40, suggesting that the activity of beta 2-adrenoceptor agonist is mediated through T lymphocyte or monocyte modulation. Fenoterol also inhibited the PHA-induced IFN-gamma production by T lymphocytes. Analogues of cAMP or activator of PKA also elicited an increase in IgE production. Moreover, the effect of fenoterol on IgE production was suppressed in the presence of PKA inhibitor. Salbutamol also potentiated the IL-4-induced IgE production from murine splenocytes activated by LPS. Furthermore, mice sensitized to ovalbumin elicited increased IgE responses after daily injection of salbutamol. This was accompanied by an increased in cytokines of Th2 subtypes. Our results showed that beta 2-adrenoceptor agonist, which are currently used in the treatment of asthma, potentiate the IgE production in vitro and in vivo.

Adrenergic beta-2 Receptor Agonists↗
PubMed1994

Effects of isozyme-selective phosphodiesterase inhibitors on eosinophil infiltration in the guinea-pig lung.

The effects of selective phosphodiesterase isozyme inhibitors on eosinophil infiltration induced by antigen challenge or by exposure to an aerosol of platelet-activating factor (PAF) were investigated in the guinea-pig. Pretreatment 24 h and 3 h before antigen challenge or PAF exposure with theophylline (100 mg/kg), rolipram (5 mg/kg) and Ro 20-1724 (30 mg/kg) significantly reduced the increase in eosinophil numbers in bronchoalveolar lavage fluid. In contrast, milrinone, SK&F 94-120 and zaprinast were ineffective against antigen-induced eosinophil recruitment. Theophylline, rolipram and Ro 20-1724 also significantly reduced the release of eosinophil peroxidase into the bronchoalveolar lavage fluid. It is suggested that inhibitors of type IV phosphodiesterase have anti-inflammatory effects in the airways and may be useful in the treatment of asthma.

Aerosols↗
PubMed1994

Long-lasting inhibitory activity of the hetrazepinic BN 50730 on exudation and cellular alterations evoked by PAF and LPS.

1. Inhibitory effects of the hetrazepinic derivative BN 50730 on the rat pleural inflammatory response, triggered by PAF or lipopolysaccharides (LPS), were examined. The type of pharmacological blockade exerted by this antagonist in in vitro assays of eosinophil chemotaxis and platelet aggregation were also investigated. 2. Intrathoracic injection of PAF (1 microgram per cavity) caused a 4 fold increase in the extravasated protein within 15 min and led to a marked eosinophil accumulation 24 h post-challenge. BN 50730 (0.5-10 micrograms per cavity) inhibited exudation by PAF dose-dependently without modifying the response induced by histamine, bradykinin or 5-hydroxytryptamine (5-HT). 3. The kinetics of the inhibitory effect on exudation revealed that the actions of WEB 2086 and BN 52021 (10 micrograms per cavity) were over within 2 and 4 h respectively, whereas BN 50730 (10 micrograms per cavity) retained 80% of its inhibitory activity for 4 days. 4. Oral treatment with BN 50730 (10-20 mg kg-1, 1 h beforehand) suppressed the leucocyte accumulation and late eosinophilia observed 6 and 24 h after PAF respectively, but did not modify the eosinophilia induced by leukotriene B4 (LTB4) or bradykinin. BN 50730 also failed to reduce the eosinophil accumulation induced by LPS but drastically inhibited the neutrophil influx. 5. The pre-incubation of rat peritoneal eosinophils for 10 min with BN 50730 (30 nM-1 microM) dose-dependently inhibited the chemotaxis induced by PAF (0.1 microM) in vitro. The IC50 values for BN 52021, WEB 2086 and BN 50730 in this system were 5, 5 and 0.05 microM respectively. 6. In separate assays, rat peritoneal eosinophils and rabbit washed platelets were preincubated with BN 50730 or WEB 2086 (1 pM) then subjected to a series of at least two consecutive washings in order to remove the antagonist from the receptor environment. Under such conditions, only the cells pretreated with WEB 2086 recovered the sensitivity to the lipid.7. We conclude that BN 50730 is a potent, specific and long-acting PAF antagonist and its effect seems to result from a high affinity and non-competitive interaction of the drug with the PAF receptor.

Animals↗
PubMed1994

Modulation of IgE production in the mouse by beta 2-adrenoceptor agonist.

The present study examined the in vitro and in vivo effect of salbutamol on IgE production in the mouse. The present results show that salbutamol potentiates the in vitro interleukin 4 (IL-4)-induced IgE production from lipopolysaccharide-activated murine B lymphocytes. This effect is dose-dependent and is observed at concentrations above 10 nM. In vivo, when ovalbumin (OA)-sensitized BALB/c mice were treated with a daily injection of salbutamol, an increase of the anti-OA IgE levels in the serum was observed as compared to sensitized animals. Such an effect was observed at doses above 1 microgram/kg and was maximal at 10 micrograms/kg. Treatment of sensitized mice with salbutamol increased the ex vivo production of IL-4, IL-5, IL-6 and IL-10 from concanavalin A-activated splenocytes whereas no modification of IFN-gamma synthesis was noticed as compared to nontreated sensitized control mice. These results demonstrate that beta 2-adrenoceptor agonist stimulation results in an increase in IgE production both in vitro and in vivo in the mice. At least in vivo, they also suggest that the effect of this drug could be explained by an increase of the production of Th2-type lymphokines.

Albuterol↗