Inhaled budesonide fails to inhibit the PAF-induced increase in plasma leukotriene B4 in man.
1. We studied the ability of inhaled budesonide to modulate PAF-induced acute effects in nine healthy nonsmoking volunteers. Responses in inflammatory cells and mediators in peripheral blood as well as in pulmonary function and circulation were monitored. 2. Inhalation of increasing doses of PAF (total cumulative dose of 500 micrograms) caused a rapid and profound decrease in circulating white blood cells, especially in granulocytes (P less than 0.01), which was turned to an increased number of these cells (P less than 0.05, P less than 0.025, respectively) in the blood samples taken 8 min after completion of the PAF challenge. No changes in the circulating platelets or their thromboxane production were found. Plasma concentrations of histamine or methylhistamine remained unchanged during PAF-inhalation, while plasma LTB4 tripled from the baseline level at 10 min (P less than 0.0005) and was returned to the pre-PAF value at 60 min. 3. PAF inhalation induced a bronchial obstruction (P less than 0.025), but no bronchial hyperresponsiveness to methacholine was found in any of our subjects when measured 24 h after the PAF challenge. Furthermore, PAF caused a decrease in systolic blood pressure (P less than 0.05). 4. Budesonide pretreatment of 400 micrograms twice daily during the preceding 5 days had no effect on any PAF-induced events measured in our study. That fact may also contradict the role of bronchial resident or alveolar cells as a source of the PAF-induced LTB4 burst in plasma. 5. We conclude that in healthy volunteers inhaled PAF induces a marked increase in plasma LTB4, which is not inhibited by inhaled budesonide.(ABSTRACT TRUNCATED AT 250 WORDS)
Nieminen
M M
MM
Department of Pulmonary Diseases, Tampere University Hospital, Finland.
Moilanen
E K
EK
Koskinen
M O
MO
Karvonen
J I
JI
Tuomisto
L
L
Metsä-Ketelä
T J
TJ
Vapaatalo
H
H
D000280:Administration, Inhalation; D000328:Adult; D001792:Blood Platelets / Q000378:metabolism; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019819:Budesonide; D002395:Catecholamines / Q000097:blood; D004357:Drug Synergism; D005260:Female; D006632:Histamine / Q000097:blood; D006801:Humans; D007975:Leukotriene B4 / Q000097:blood*; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D008875:Middle Aged; D010972:Platelet Activating Factor / Q000494:pharmacology*; D010976:Platelet Count; D011282:Pregnenediones / Q000008:administration & dosage / Q000494:pharmacology*; D012016:Reference Values; D013929:Thromboxane B2 / Q000096:biosynthesis / Q000097:blood
D001993:Bronchodilator Agents; D002395:Catecholamines; D010972:Platelet Activating Factor; D011282:Pregnenediones; D016210:Methacholine Chloride; D007975:Leukotriene B4; D019819:Budesonide; D013929:Thromboxane B2; D006632:Histamine