Salmeterol, a long-acting beta(2)-adrenoreceptor agonist without known
immunotoxicity, was studied in a 28-day repeated dose toxicity test i
n Wistar rats. Several immunotoxicity screening parameters were incorp
orated in the study protocol to investigate the immunotoxic potential
of the compound. Male rats were orally treated with 0, 0.2, 2 and 20 m
g salmeterol/kg body weight/day. At the 20 mg/kg/day dose level, intub
ation errors occurred because the animals tried to resist intubation.
Some of these animals died intercurrently. Therefore, the magnitude of
the dose was lowered to 10 mg/kg/day at day 9 of treatment. Body weig
ht and bone marrow cellularity were not affected. Hematological parame
ters were not altered either, except for platelet counts, that were de
creased at all dose levels. Also liver weights were decreased at all d
ose levels tested. Absolute thymic weights were decreased at the 2 and
20/10 mg/kg/day dose levels. No treatment-related (histo)pathological
lesions were seen in the (non)lymphoid organs. Serum IgM levels were
increased at the 0.2, and Ige at the 2 and 20/10 mg/kg/day dose levels
, respectively. B cell numbers in the spleen were decreased at all dos
e levels tested. The data indicate that the test battery applied to sa
lmeterol is able to detect low immunotoxic potential. Further research
is needed to elucidate whether salmeterol interferes with immune resp
onses in rats upon antigenic challenge. Copyright (C) 1996 Internation
al Society for Immunopharmacology.