I Azevedo, J de Blic, P Scheinmann, BB Vargaftig and M Bachelet
Unite de Pharmacologie Cellulaire, Unite Associee Institut Pasteur- INSERM, Paris, France.

To test the hypothesis that alveolar macrophages (AM) from wheezy infants release increased amounts of eicosanoids, as do AM from adults with asthma, we compared eicosanoid release by unstimulated- and ionophore-A23187-stimulated AM from 13 wheezy and six nonwheezy infants and analyzed its regulation by dexamethasone in vitro. Alveolar macrophages from wheezy infants released greater amounts of thromboxane A2 (TxA2) and leukotriene B4 (LTB4) under resting conditions and of TxA2 upon stimulation than did those from control subjects. Dexamethasone induced a dose-dependent inhibition of the spontaneous and A23187-stimulated release of TxA2, but not of the A23187-stimulated release of lipoxygenase products. The inhibition of TxA2 formation was maintained when free arachidonic acid was added during A23187 stimulation, demonstrating that dexamethasone acted mainly at a postphospholipase A2 site. AM exposed to acetylsalicylate and then incubated overnight exhibited de novo cyclooxygenase synthesis, suggesting the presence of the inducible cyclooxygenase as a target for inhibition by dexamethasone. In conclusion, our findings suggest that AM from wheezy infants are activated in vivo to release eicosanoids, as are AM from asthmatic adults, and they support the therapeutic indications of glucocorticoids in severe recurrent wheezing of infancy.

This article has been cited by other articles:

				E. Migoya, G. L. Kearns, A. Hartford, J. Zhao, J. van Adelsberg, C. A. Tozzi, B. Knorr, and P. Deutsch Pharmacokinetics of Montelukast in Asthmatic Patients 6 to 24 Months Old J. Clin. Pharmacol., May 1, 2004; 44(5): 487 - 494. [Abstract] [Full Text]

				F. Kanniess, K. Richter, S. Janicki, M.B. Schleiss, R.A. Jorres, and H. Magnussen Dose reduction of inhaled corticosteroids under concomitant medication with montelukast in patients with asthma Eur. Respir. J., November 1, 2002; 20(5): 1080 - 1087. [Abstract] [Full Text] [PDF]

				M. Le Bourgeois, M. Goncalves, L. Le Clainche, M.-R. Benoist, J.-C. Fournet, P. Scheinmann, and J. de Blic Bronchoalveolar Cells in Children < 3 Years Old With Severe Recurrent Wheezing* Chest, September 1, 2002; 122(3): 791 - 797. [Abstract] [Full Text] [PDF]

				S. S. Salvi, M. T. Krishna, A. P. Sampson, and S. T. Holgate The Anti-inflammatory Effects of Leukotriene-Modifying Drugs and Their Use in Asthma Chest, May 1, 2001; 119(5): 1533 - 1546. [Abstract] [Full Text] [PDF]

				H. Bisgaard Leukotriene Modifiers in Pediatric Asthma Management Pediatrics, February 1, 2001; 107(2): 381 - 390. [Abstract] [Full Text]

				K. A. McGill, C. A. Sorkness, C. Ferguson-Page, J. E. Gern, T. C. Havighurst, B. Knipfer, R. F. Lemanske Jr., and W. W. Busse Asthma in Non-Inner City Head Start Children Pediatrics, July 1, 1998; 102(1): 77 - 83. [Abstract] [Full Text]