[Effect of eosinophil apoptosis on glucocorticoid-resistant asthma].
OBJECTIVE
To investigate the function of eosinophil apoptosis and regulation of glucocortico steroids on IL-5 and GM-CSF expression in peripheral blood mononuclear cells (PBMCs) in glucocorticoid-resistant asthmatic patients.


METHODS
Eosinophils (EOS) and PBMCs isolated from glucocorticoid-sensitive (SS, 15 cases) and resistant (SR, 30 cases) asthmatic subjects were cultured and treated with dexamethasone (DXM) in vitro. Concentrations of IL-5 and GM-CSF were determined by ELISA in the supernatants recovered in sham and DXM treated cells. The rates of EOS apoptosis and Fas antigen expression were documented via flow cytometer in sham, DXM treated and PBMC supernatant treated groups respectively.


RESULTS
There were no statistical significant differences of the concentrations of both IL-5 and GM-CSF in sham cultured PBMC supernatants between SS and SR groups [(196 +/- 68) micrograms/L vs. (235 +/- 98) micrograms/L IL-5 (P > 0.05), (325 +/- 110) micrograms/L vs. (356 +/- 131) micrograms/L GM-CSF (P > 0.05); SS versus SR groups, respectively]. There were statistically significant decreases in both IL-5 and GM-CSF after DXM exposure in SS group [(196 +/- 68) micrograms/L vs. (147 +/- 62) micrograms/L IL-5 (P < 0.01); (325 +/- 110) micrograms/L vs. (270 +/- 97) micrograms/L GM-CSF (P < 0.01)]. In contrast, there were no significant differences in both IL-5 and GM-CSF after DXM exposure in SR group. Baseline rates of both EOS apoptosis and Fas antigen expression were statistically significant different between SS and SR groups [(67 +/- 21)% vs. (33 +/- 17)% the rate of EOS apoptosis (P < 0.001); (54 +/- 23)% vs. (27 +/- 15)% the rate of Fas antigen expression (P < 0.001), SS versus SR groups, respectively]. A dramatic increase in EOS apoptosis after DXM exposure was observed in SS group [(67 +/- 21)% vs. (89 +/- 20)% (P < 0.01), baseline vs. DXM exposure, respectively], but there was no significant change in Fas antigen expression. There were no significant changes in both EOS apoptosis and Fas antigen expression in SR group after DXM exposure.


CONCLUSIONS
These data suggest that EOS compromised apoptosis might exist and could not be affected by glucocorticoid induction in SR asthma. On the other hand, Th2 cytokine over-expression could not be inhibited by glucocorticoid in SR group in vitro.
Liu
C
C
Division of Respiratory Medicine, The First Hospital of West China University of Medical Sciences, Chengdu 610041, China.
Wang
Z
Z
Xie
M
M
D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D017209:Apoptosis; D001249:Asthma / Q000188:drug therapy / Q000473:pathology*; D004351:Drug Resistance; D004804:Eosinophils / Q000502:physiology*; D005938:Glucocorticoids / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D015848:Interleukin-5 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology; D019014:fas Receptor / Q000096:biosynthesis
D018927:Anti-Asthmatic Agents; D005938:Glucocorticoids; D015848:Interleukin-5; D019014:fas Receptor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor