Bf. Gibbs et al., Ambroxol inhibits the release of histamine, leukotrienes and cytokines from human leukocytes and mast cells, INFLAMM RES, 48(2), 1999, pp. 86-93
Objectives and Design: The effects of the mucolytic agents ambroxol and N-a
cetylcystein (NAC) were studied on the release of histamine, leukotrienes,
cytokines and superoxide anions from a variety of cells involved in the pat
hogenesis of allergic inflammation.
Subjects: Mast cells were isolated from human adenoids and skin (n = 5-6).
Basophils, monocytes and granulocytes were obtained from Buffy-coat blood o
btained from healthy blood donors (n = 4-7) and enriched by density centrif
ugation.
Treatment and Methods: Ambroxol or NAC were added to the cells for differen
t periods before stimulation with various immunological and non-immunologic
al secretagogues. Histamine release from mast cells, basophils and monocyte
s was assayed either by radioimmunoassay or spectrofluorometrically. LTC4 (
basophils), LTB4 (neutrophil/eosinophil granulocytes or monocytes), IL-4 an
d IL-13 (basophils) were measured by ELISA.
Results: Ambroxol inhibited histamine release by more than 50% from human a
denoidal mast cells (1000 mu M ambroxol) and skin mast cells (100 mu M ambr
oxol) stimulated by Con A and compound 48/80, respectively. Ambroxol (100 m
u M) strikingly inhibited anti-IgE induced release of both histamine, LTC4,
IL-4 and IL-13 from basophils and reduced both histamine and LTB4 release
induced by C5a or Zymosan in monocytes. The drug also reduced LTB4 and supe
roxide anion production in granulocytes stimulated by zymosan or fMLP. In a
ll cell types studied, ambroxol was more efficacious following a short prei
ncubation (5-15 min) of the drug with the cells before stimulation. In cont
rast, NAC produced no clear effects on any of the different cell types stud
ied, regardless of the preincubation period, the concentration or the stimu
lus employed.
Conclusions: Unlike NAG, ambroxol is able to not only inhibit acute mediato
r release from mast cells and leukocytes but also reduce immunomodulatory c
ytokine generation from basophils and may have beneficial effects in the tr
eatment of allergic respiratory diseases.