The effect of treatment with budesonide or PGE2 in vitro on allergen-induced increases in canine bone marrow progenitors.
Increased bone marrow granulocyte-macrophage colony forming units (GM-CFU) in dogs developing allergen-induced airway hyperresponsiveness can be accounted for by a factor(s) present in serum following the allergen challenge. The present study evaluated whether in vitro treatment of bone marrow with budesonide or prostaglandin (PG)E2, prevents allergen-induced bone marrow stimulation. Eight dogs were studied after allergen and diluent inhalation challenges. Budesonide (10[-7] M) or PGE2 (10[-6] M) was added to bone marrow aspirated 24 h after challenge. Budesonide or PGE2 was also added to bone marrow aspirated before challenge, to which serum taken 24 h after challenge was subsequently added. Non-adherent mononuclear bone marrow cells were incubated in the presence of the serum and granulocyte/macrophage colony stimulating factor (GM-CSF), granulocyte stimulating factor (G-CSF), or stem cell factor (SCF), and the number of GM-CFU counted. Allergen-induced increases in the number of GM-CFU in bone marrow aspirated 24 h after allergen (P < 0.001) were not attenuated by budesonide or PGE2 treatment (P > 0.05). However, GM-CFU increases in bone marrow aspirated before challenge and incubated with post-allergen challenge serum (P < 0.001) were blocked by either budesonide or PGE2 (P < 0.001). These findings demonstrate that budesonide and PGE2 can act directly on the bone marrow, preventing allergen-induced increases in inflammatory cell progenitor production. This suggests that the bone marrow must be considered as a possible site of action for drugs which attenuate allergen-induced asthmatic responses.
Inman
M D
MD
Asthma Research Group, McMaster University, Hamilton, Ontario, Canada.
Denburg
J A
JA
Ellis
R
R
Dahlbäck
M
M
O'Byrne
P M
PM
D000485:Allergens / Q000008:administration & dosage*; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D019819:Budesonide / Q000494:pharmacology*; D002452:Cell Count / Q000187:drug effects; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology*; D004285:Dogs; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology*; D010120:Oxytocics / Q000494:pharmacology*
D000485:Allergens; D001993:Bronchodilator Agents; D010120:Oxytocics; D019819:Budesonide; D015232:Dinoprostone