Immunomodulators such as
cyclosporin A (CsA) and
SAR943 (32-deoxorapamycin) inhibit single
allergen-induced allergic
inflammation such as eosinophilic and lymphocytic infiltration and
mRNA expression for
interleukin (IL)-4 and
IL-5. We examined the effects of CsA and
SAR943, administered orally, on asthmatic responses in a rat model of chronic allergic
inflammation. Sensitized Brown-Norway (BN) rats were exposed to
ovalbumin (OVA)
aerosol every third day on six occasions. CsA (5 mg/kg/day),
SAR943 (2.5 mg/kg/day) or vehicle (
Neoral) was administered orally, once a day, from days 10 to 21 (a total of 12 doses). We measured eosinophilic and T-cell
inflammation in the airways, proliferation of airway cells by incorporation of
bromodeoxyuridine (
BrdU) and bronchial responsiveness to
acetylcholine. CsA had no effects, while
SAR943 inhibited airway smooth muscle (ASM, P < 0.05) and epithelial cell (P < 0.01)
BrdU incorporation, and the number of CD4+ T cells (P < 0.05), without effects on BHR. ASM thickness was not significantly increased following chronic
allergen exposure. Therefore, CsA and
SAR943 have no effect on chronic eosinophilic
inflammation, while
SAR943, but not CsA, had a small effect on the proliferation of ASM and epithelium.