Pharmacological modulation of a model of bronchial inflammation after aerosol-induced active anaphylactic shock in conscious guinea pigs

Tarayre, J P; Aliaga, M.; Barbara, M.; Tisseyre, N.; Vieu, Sylvie; Tisné-Versailles, J

doi:10.1016/0192-0561(91)90004-q

Cited by 9 publications

(10 citation statements)

References 36 publications

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“…These findings suggest that the anti-inflammatory properties of cromolyn are complex and its mechanism of action may involve other targets in addition to mast cells (Bernstein & Bernstein, 1993). The results of our study are in accordance with other data from the literature, where it was demonstrated that this drug markedly inhibited both microvascular leakage and cell migration in several models of bronchial hyperreactivity (Pauwels, 1989;Tarayre et al, 1991). Taken together, the results presented here do not permit us to suggest the precise mechanism by which cromolyn is exerting its anti-inflammatory effects, but one cannot discard the possibility that this drug may be acting in one or several steps of neurogenic inflammation as has been recently proposed (Kowaski et al, 1990;Holian et al, 1991).…”

Section: Discussionsupporting

confidence: 82%

Anti‐inflammatory effects of theophylline, cromolyn and salbutamol in a murine model of pleurisy

Saleh

Calixto

Medeiros

1996

British J Pharmacology

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1 The aim of this study was to examine the effect of theophylline, cromolyn and salbutamol, three wellknown anti-asthmatic drugs, on the early (4 h) and late (48 h) phases of cell migration and fluid leakage induced by carrageenin in the pleural cavity of mice. 2 In the first set of experiments, animals were pretreated (30 min) with different doses of theophylline (0.5-50 mg kg-', i.p.), cromolyn (0.02-0.2 mg per pleural cavity) or salbutamol (0.05-50 mg kg-', i.p.); the total and differential cell content, and also the exudate were analysed 4 h after carrageenin (1 %) administration. Afterwards, in order to evaluate the time course effects of these drugs on both phases of the inflammatory reaction, one dose employed in the above protocol was chosen, to pretreat (0.5-24 h) different groups of animals. The studied parameters were evaluated 4 and 48 h after pleurisy induction. 3 Acute administration of theophylline (1-50 mg kg-1, i.p.), cromolyn (0.02-0.2 mg per pleural cavity) and salbutamol (0.5-50 mg kg-', i.p.), 30 min prior to carrageenin, caused significant inhibition of total cell and fluid leakage in the pleural cavity at 4 h (P<0.01). All drugs exerted a long-lasting inhibitory effect on both exudation and cell migration (P<0.01) when administered 0.5-8 h before pleurisy induction. However, the temporal profile of the inhibitory effect induced by these drugs on the first phase of the inflammatory reaction was clearly different. Thus, the inhibitory effect induced by theophylline and cromolyn on exudation was significantly longer (up to 24 h) in comparison to their effects on cell migration (only up to 8 h). In contrast, although salbutamol when administered 30 min before pleurisy induction abolished fluid leakage (P<0.01), this effect was not sustained in the groups pretreated for 4-8 h. In these latter groups, a significant but much smaller reduction of exudation was observed (P<0.01), whereas the magnitude of cell migration inhibition did not vary. 4 The second phase (48 h) of the inflammatory reaction induced by carrageenin (1%) was significantly inhibited by cromolyn (0.02 mg per pleural cavity) when this drug was administered 0.5-24 h before pleurisy induction (P<0.01). Similar results were observed when theophylline (50 mg kg-', i.p.) was administered 0.5-4 h before the injection of the phlogistic agent (P<0.01). Treatment of the animals with salbutamol (5 mg kg-', i.p.), 0.5-24 h before pleurisy induction, did not inhibit either cell migration or fluid leakage. In this condition, a significant increase of these parameters was observed in the group pretreated with salbutamol 8-24 h before pleurisy induction (P<0.01). 5 These results indicate that theophylline and cromolyn were able to inhibit the early (4 h) and late (48 h) phases of the inflammatory reaction induced by carrageenin in a murine model of pleurisy. Salbutamol was effective only against the early phase. The inhibitory effects of theophylline, cromolyn and salbutamol on the early phase of this inflammatory reaction were long-lasting, ...

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Section: Discussionsupporting

confidence: 82%

Anti‐inflammatory effects of theophylline, cromolyn and salbutamol in a murine model of pleurisy

Saleh

Calixto

Medeiros

1996

British J Pharmacology

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“…TARAYRE and co-workers [73][74][75] investigated, both in rats and in guinea-pigs, the effect of theophylline on the influx of inflammatory cells in the airways of sensitized animals 24 h after exposure to an aerosolized antigen. In guinea-pigs, treatment with theophylline 5 min and 5 h after the aerosol exposure significantly inhibited the eosinophilic infiltration of the airways.…”

Section: Animal Modelsmentioning

confidence: 99%

“…Theophylline also inhibits interferon-gamma induced expression of IL-2-receptors on a cultured lymphocyte line [100]. An inhibitory effect on T-lymphocyte induced cytokine release may account for the inhibitory effect of theophylline on the influx of inflammatory cells after inhaled allergen in animal models [72][73][74][75][76][77][78].…”

Section: Eosinophils the Effect Of Theophylline On Eosinophil Cell Fmentioning

confidence: 99%

Theophylline in the management of asthma: time for reappraisal?

Barnes¹,

Pauwels²

1994

Eur Respir J

249

107

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T Th he eo op ph hy yl ll li in ne e i in n t th he e m ma an na ag ge em me en nt t o of f a as st th hm ma a: : t ti im me e f fo or r r re ea ap pp pr ra ai is sa al l? ?P.J. Barnes*, R.A. Pauwels** Theophylline is now considered to be a bronchodilator, but it is increasingly recognized that theophylline has other anti-asthma activities, which may be more important. Theophylline, even at low plasma concentrations, inhibits the late asthmatic reaction following allergen challenge. These clinical pharmacological observations are substantiated by experimental animal and in vitro data showing that theophylline has several anti-inflammatory activities relevant to asthma. These include the inhibition of cytokine synthesis and release, the inhibition of inflammatory cell activation and microvascular leakage, and the prevention of airway hyperresponsiveness induced by airway inflammation. Theophylline appears to have immunomodulatory effects, even at relatively low plasma concentrations.Based on these considerations, theophylline can be regarded as a useful alternative to other anti-inflammatory drugs for the chronic treatment of mild to moderate asthma. Theophylline should be used at lower doses to achieve plasma concentrations of 5-10 mg·l -1 , which will avoid the risk of side-effects.Further studies are required to evaluate the role of low-dose theophylline as an adjunct to low-dose inhaled steroids in the management of chronic asthma. It may now be appropriate to re-evaluate the role of theophylline in asthma management.

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“…These anti-inflammatory and immunomodulatory effects of xanthines have also been observed in vivo in animal models and also in humans. In the guinea-pig, it has been shown that xanthines attenuate airway hyperresponsiveness [5] and the late response in sensitized animals [6]. They also inhibit eosinophil infiltration into guinea-pig airways [7].…”

mentioning

confidence: 99%