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Am. J. Respir. Cell Mol. Biol., Volume 25, Number 6, December, 2001 751-760

CTLA4-IgG Reverses Asthma Manifestations in a Mild but Not in a More "Severe" Ongoing Murine Model

Daphne T. Deurloo, Betty C.A.M. van Esch, Claudia L. Hofstra, Frans P. Nijkamp, and Antoon J.M. van Oosterhout

Department of Pharmacology and Pathophysiology, Faculty of Pharmacy, Utrecht University, Utrecht, The Netherlands

We investigated whether CTLA4-Ig can reverse established asthma manifestations in a novel murine model of ongoing disease. In BALB/c mice, sensitized to ovalbumin (OVA) without adjuvant, airway inflammation was induced by a first series of OVA aerosol challenges. Murine CTLA4-IgG was then administered, followed by a second series of OVA inhalations. In control-treated mice, two series of OVA challenges induced upregulation of OVA-specific IgE in serum, eosinophils in the bronchoalveolar lavage fluid (BALF), and IL-5 production by lung lymphocytes upon OVA restimulation in vitro, compared with saline-challenged mice. CTLA4-IgG significantly inhibited all of these parameters in OVA-challenged mice. Importantly, mCTLA4-IgG performed better than the gold-standard dexamethasone because this corticosteroid did not inhibit the upregulation of OVA-specific IgE in serum. In a more "severe" ongoing model, induced by sensitization to OVA emulsified in aluminum hydroxide, resulting in airway hyperresponsiveness to methacholine and stronger inflammatory responses, mCTLA4-IgG was less effective in that only the number of eosinophils in the BALF was reduced (P = 0.053), whereas dexamethasone inhibited both BALF eosinophilia and cytokine production by lung lymphocytes. Thus, CTLA4-Ig might be an effective alternative therapy in established allergic asthma, especially in situations of mild disease.

Abbreviations: aluminum hydroxide, alum; bronchoalveolar lavage fluid, BALF; digoxigenin, DIG; dose-response curve, DRC; fetal calf serum, FCS; ovalbumin, OVA; phosphate-buffered saline, PBS; standard error of the mean, SEM; T-cell receptor, TCR.




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Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2001 American Thoracic Society.