Effects of Theophylline Compared with Prednisolone on Late Phase Airway Leukocyte Infiltration in Guinea Pigs

Gristwood, R. W.; Llupiá, J; Fernández, A. Gómez-Bastero; Berga, P.

doi:10.1159/000235388

Cited by 20 publications

(18 citation statements)

References 6 publications

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“…Our results contrast with those of others (Gristwood et al, 1991;Schudt et al, 1991;Underwood et al, 1993) who have demonstrated inhibitory effects on eosinophil accumulation by acute administration of PDE inhibitors. However, such differences may be attributable to differences in methodology between these studies and ours.…”

Section: Discussioncontrasting

confidence: 99%

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Acute versus chronic administration of phosphodiesterase inhibitors on allergen‐induced pulmonary cell influx in sensitized guinea‐pigs

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1995

British J Pharmacology

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The aims of this study were to determine which phosphodiesterase (PDE) isoenzymes are involved in the control of eosinophil accumulation in the airways of ovalbumin (OVA)‐immunized guinea‐pigs by the use of isoenzyme selective inhibitors and to compare the effects of acute versus chronic administration of PDE isozyme inhibitors on pulmonary cell influx in ovalbumin‐immunized guinea‐pigs. Guinea‐pigs were sensitized and subsequently challenged with aerosolized OVA. Twenty four hours later bronchoalveolar lavage (BAL) was performed to permit assessment of inflammatory cell accumulation. A significant increase in the number of eosinophils was observed in the lavage fluid from OVA‐immunized (13.6 ± 1.4 × 104ml−1 in acute experiments and 10.1 ± 1.4 × 104 ml−1 in chronic experiments) animals compared with sham‐treated controls (5.6 ± 0.6 × 104 ml−1 in acute experiments and 5.1 ± 0.6 × 104 ml−1 in chronic experiments). There was no difference in neutrophil, mononuclear cell or total cell numbers between the two groups. Acute administration of a high dose of selective and non‐selective PDE inhibitors by the i.p. route had no significant effect on eosinophil accumulation in the airways. Chronic administration of a low dose (3 mg kg−1, i.p., twice daily for 7 days) of the type IV PDE inhibitor, RO 20–1724, and the PDE III/IV inhibitor, zardaverine, produced a significant inhibition of eosinophil accumulation (46% and 59% respectively). These results suggest that the type IV PDE isoenzyme plays a role in the control of allergen‐induced eosinophil infiltration into the airways, but indicate that a period of low dose chronic treatment with a type IV or mixed type III/IV PDE inhibitor is necessary for eosinophil accumulation in the airways to be reduced.

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Section: Discussioncontrasting

confidence: 99%

“…Acute administration of theophylline and selective PDE isoenzyme inhibitors has been reported to reduce eosinophil infiltration induced by allergen challenge in sensitized guineapigs (Gristwood et al, 1991;Schudt et al, 1991;Manzini et al, 1993;Underwood et al, 1993 Pharmacology (1995) 114. 93-98 .…”

Section: Introductionmentioning

confidence: 99%

Acute versus chronic administration of phosphodiesterase inhibitors on allergen‐induced pulmonary cell influx in sensitized guinea‐pigs

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1995

British J Pharmacology

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“…The inhibitory activity of PKA on rho activation in leukocytes may thus help explain the ability of some cAMP-elevating drugs to inhibit leukocyte transendothelial migration in vitro and recruitment and homing in vivo (17)(18)(19)(20)(21), phenomena that are dependent on chemoattractants and integrins. The effect may also permit cross-talk between pro-adhesive and anti-adhesive heterotrimeric G protein-linked receptors, potentially contributing, for example, to the inhibition of chemoattractant-induced neutrophil migration by adenosine, prostaglandin E1, or ␤ 2 -adrenergic receptors (22,23), G␣ s -linked serpentine receptors that activate adenylyl cyclase to produce cAMP.…”

mentioning

confidence: 99%

Elevation of Intracellular cAMP Inhibits RhoA Activation and Integrin-dependent Leukocyte Adhesion Induced by Chemoattractants

Laudanna

Campbell

Butcher

1997

Journal of Biological Chemistry

198

144

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Chemoattractant receptors of the serpentine, heterotrimeric G␣ i protein-linked family can activate leukocyte integrins and in this role regulate leukocyte traffic and cell-cell interactions in immune and inflammatory responses. Using a mouse lymphoid cell line transfected with human formyl peptide or interleukin-8 receptors and normal human neutrophils as models, we show that cAMP functions as a gating element on the chemoattractant-induced rho-dependent signaling pathway leading to leukocyte integrin activation and adhesion. cAMP, acting through protein kinase A, inhibits chemoattractant-triggered integrin-dependent leukocyte adhesion. cAMP also prevents guanine nucleotide exchange on RhoA, a small GTP-binding protein of the rho subfamily, which is activated in seconds by chemoattractants. In contrast, chemoattractant-triggered intracellular calcium elevation is unaffected by cAMP, and cAMP has no effect on rho-dependent adhesion and RhoA guanine nucleotide exchange triggered through the independent protein kinase C pathway. These data suggest that cAMP-induced inhibition of rho activation may be responsible for the anti-adhesive effect of cAMP and may contribute to the anti-inflammatory activity of cAMP elevating agonists and drugs. Moreover, the findings extend the concept of cyclic nucleotide gating as a broadly important mechanism in the regulation of intracellular signaling pathways and the cellular activities they control.

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“…It is therefore possible that inhibition of antigen-induced AHR by rolipram may be due to modulation of C-fibre activity to reduce tachykinin release. Furthermore, this may explain the inhibitory effect of rolipram on ozone-induced AHR to inhaled histamine (Holbrook & Hughes, 1992) where the AHR is capsaicin sensitive and thought to be due to increased tachykinin effects resulting from oxidant damage of airway lumen neutral endopeptidase (Yeadon et al, 1992 (Griswood et al, 1991;Underwood et al, 1994;Lagente et al, 1994) and primate (Turner et al, 1994). Surprisingly, rolipram had no effect on neutrophil recruitment.…”

Section: Discussionmentioning

confidence: 99%

Effects of theophylline and rolipram on antigen‐induced airway responses in neonatally immunized rabbits

Gozzard¹,

Herd²,

Blake³

et al. 1996

British J Pharmacology

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1 The effects of the xanthine, theophylline, a non-selective phosphodiesterase (PDE) inhibitor, and the phosphodiesterase type 4 (PDE 4) inhibitor, rolipram, were evaluated in a model of antigen-induced airway responses in the allergic rabbit. 2 Adult litter-matched NZW rabbits (2.5-3.9 kg), immunized within 24 h of birth with Alternaria tenuis antigen, were pretreated twice daily for 3 days with theophylline (3 mg kg-', i.p.) or rolipram (1 mg kg-', i.p.) prior to antigen challenge (Alternaria tenuis). For each drug-treated group, a parallel group of rabbits were pretreated with the appropriate vehicle. In all groups airway responsiveness to inhaled histamine and bronchoalveolar lavage (BAL) was performed 24 h before and after antigen-challenge. 3 Basal lung function in terms of resistance (RL, cmH2O 11 s-1) and dynamic compliance (Cdyf, ml cmH2O ') were unaltered by pretreatment with theophylline or rolipram compared to their respective vehicles 24 h prior to or post antigen challenge. 4 The acute bronchoconstriction induced by inhaled Alternaria tenuis aerosol was unaffected by pretreatment with theophylline or rolipram. 5 Airway hyperresponsiveness to inhaled histamine was indicated by reduced RL PC50 (2.4-3.5 fold) and Cdyn PC35 (2.5-2.6 fold) values 24 h after antigen challenge. Treatment with rolipram, but not theophylline, prevented the increase in responsiveness to inhaled histamine 24 h after antigen challenge. 6 Total cells per ml of BAL fluid increased 24 h after antigen challenge due to the recruitment of neutrophils and eosinophils. Antigen-induced increases in pulmonary neutrophils were unaffected; however, eosinophils were reduced 57.5% in theophylline and 82% in rolipram-treated rabbits. 7 Inhalation of Alternaria tenuis aerosol elicits an acute bronchoconstriction, followed 24 h later by an increased responsiveness to inhaled histamine and pulmonary neutrophil and eosinophil recruitment in the immunized rabbit. With the dosing regimes used, both rolipram and theophylline inhibited eosinophil recruitment, whilst only rolipram prevented the development of airway hyperresponsiveness. Neither agent inhibited the acute bronchoconstriction due to inhaled antigen.

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Effects of Theophylline Compared with Prednisolone on Late Phase Airway Leukocyte Infiltration in Guinea Pigs

Cited by 20 publications

References 6 publications

Acute versus chronic administration of phosphodiesterase inhibitors on allergen‐induced pulmonary cell influx in sensitized guinea‐pigs

Acute versus chronic administration of phosphodiesterase inhibitors on allergen‐induced pulmonary cell influx in sensitized guinea‐pigs

Elevation of Intracellular cAMP Inhibits RhoA Activation and Integrin-dependent Leukocyte Adhesion Induced by Chemoattractants

Effects of theophylline and rolipram on antigen‐induced airway responses in neonatally immunized rabbits

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