Effects of a corticosteroid, budesonide, on alveolar macrophage and blood monocyte secretion of cytokines: differential sensitivity of GM-CSF, IL-1 beta, and IL-6.
Down-regulation of cytokine production in activated human blood monocytes (BMs) and alveolar macrophages (AMs) can be achieved in vitro by treatment with corticosteroids. The inhibition of cytokine secretion by corticosteroids may have important therapeutic consequences in e.g. asthma. However, relatively little is known about possible differences in the sensitivity of different cytokines to corticosteroid treatment. Homologous BMs and AMs were obtained from six healthy volunteers. Secretion of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the cultures of lipopolysaccharide (LPS) stimulated adherent BMs and AMs was analysed using specific immunoassays. Sensitivity of the IL-1 beta, IL-6, and GM-CSF secretion to the in vitro treatment with a synthetic corticosteroid, budesonide, was compared. BMs and AMs displayed significant differences in both cytokine secretion and susceptibility to regulation by budesonide. When added to the BM cultures concomitantly with LPS, budesonide suppressed IL-1 beta and IL-6 only partially (to 30% of the control level). In contrast, GM-CSF release in these cultures was almost totally inhibited by budesonide (> or = 10(-8) M). The IC50 for inhibition of the GM-CSF secretion was as low as 2 x 10(-10) M. In the AM cultures, budesonide had very little effect on IL-1 beta and IL-6 secretion (inhibition to 80% and 60% of control levels, respectively), while GM-CSF secretion was suppressed to 20% of control by budesonide concentrations > or = 10(-7) M.(ABSTRACT TRUNCATED AT 250 WORDS)
Linden
M
M
Preclinical Research and Development, Astra Draco AB, Lund, Sweden.
Brattsand
R
R
D019819:Budesonide; D016207:Cytokines / Q000378:metabolism*; D005938:Glucocorticoids / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D011282:Pregnenediones / Q000494:pharmacology*; D013268:Stimulation, Chemical
D016207:Cytokines; D005938:Glucocorticoids; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011282:Pregnenediones; D019819:Budesonide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor