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

被引:74
作者
LINDEN, M [1 ]
BRATTSAND, R [1 ]
机构
[1] UNIV LUND HOSP, DEPT LUNG MED, S-22185 LUND, SWEDEN
关键词
GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR; INTERLEUKIN-1-BETA; INTERLEUKIN-6; HUMAN;
D O I
10.1006/pulp.1994.1004
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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-1β (IL-1β), 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-1β, 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-1β 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 (≥ 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-1β 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 ≥ 10-7 M. These in vitro studies suggest that GM-CSF secretion from BMs and AMs is more sensitive to corticosteroid treatment than IL-1β 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. © 1994 Academic Press.
引用
收藏
页码:43 / 47
页数:5
相关论文
共 24 条
[1]   GENE-REGULATION BY STEROID-HORMONES [J].
BEATO, M .
CELL, 1989, 56 (03) :335-344
[2]   INTERLEUKIN-1 ACTS ON CULTURED HUMAN VASCULAR ENDOTHELIUM TO INCREASE THE ADHESION OF POLYMORPHONUCLEAR LEUKOCYTES, MONOCYTES, AND RELATED LEUKOCYTE CELL-LINES [J].
BEVILACQUA, MP ;
POBER, JS ;
WHEELER, ME ;
COTRAN, RS ;
GIMBRONE, MA .
JOURNAL OF CLINICAL INVESTIGATION, 1985, 76 (05) :2003-2011
[3]   DIFFERENTIAL EFFECT OF HYDROCORTISONE ON EOSINOPHIL AND NEUTROPHIL PROLIFERATION [J].
BJORNSON, BH ;
HARVEY, JM ;
ROSE, L .
JOURNAL OF CLINICAL INVESTIGATION, 1985, 76 (03) :924-929
[4]   EFFECTS OF GLUCOCORTICOIDS ON EOSINOPHIL COLONY GROWTH [J].
BUTTERFIELD, JH ;
ACKERMAN, SJ ;
WEILER, D ;
EISENBREY, AB ;
GLEICH, GJ .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 1986, 78 (03) :450-457
[5]   BIOLOGY OF INTERLEUKIN-1 [J].
DINARELLO, CA .
FASEB JOURNAL, 1988, 2 (02) :108-115
[6]   RELATIONSHIP BETWEEN CHANGED ALVEOLAR-CAPILLARY PERMEABILITY AND ANGIOTENSIN CONVERTING ENZYME-ACTIVITY IN SERUM IN SARCOIDOSIS [J].
EKLUND, A ;
BLASCHKE, E .
THORAX, 1986, 41 (08) :629-634
[7]  
GUYRE PM, 1989, ANTIINFLAMMATORY STE, P199
[8]   THE BIOLOGY OF INTERLEUKIN-6 [J].
KISHIMOTO, T .
BLOOD, 1989, 74 (01) :1-10
[9]  
LE JM, 1987, LAB INVEST, V56, P234
[10]   GLUCOCORTICOIDS SELECTIVELY INHIBIT THE TRANSCRIPTION OF THE INTERLEUKIN 1-BETA GENE AND DECREASE THE STABILITY OF INTERLEUKIN 1-BETA MESSENGER-RNA [J].
LEE, SW ;
TSOU, AP ;
CHAN, H ;
THOMAS, J ;
PETRIE, K ;
EUGUI, EM ;
ALLISON, AC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (04) :1204-1208