Effects of a Corticosteroid, Budesonide, on Alveolar Macrophage and Blood Monocyte Secretion of Cytokines: Differential Sensitivity of GM-CSF, IL-1β, and IL-6
✍ Scribed by Margareta Linden; Ralph Brattsand
- Publisher
- Elsevier
- Year
- 1994
- Tongue
- English
- Weight
- 273 KB
- Volume
- 7
- Category
- Article
- ISSN
- 0952-0600
No coin nor oath required. For personal study only.
✦ Synopsis
SUMMARY: 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 GMCSF 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 (\left(\geqslant 10^{-8} \mathrm{M}\right)). The (\mathrm{IC}_{50}) for inhibition of the GM-CSF secretion was as low as (2 \times 10^{-10} \mathrm{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 (\geqslant 10^{-7} \mathrm{M}). These in vitro studies suggest that GM-CSF secretion from BMs and AMs is more sensitive to corticosteroid treatment than IL-1 (\beta) and IL-6 secretion. Moreover, these data support the view that human monocytes derived from different compartments or at different stages of differentiation exhibit different responsiveness to corticosteroids.