Corticosteroid-induced apoptosis of eosinophils in atopic dermatitis patients.
We examined the mechanism by which steroid administration significantly decreases the high eosinophil cell count in peripheral blood in patients with atopic dermatitis (AD). Eosinophils were isolated from the peripheral blood of patients with moderate or severe adult AD, and cultured. After steroid was added to the culture medium, we examined the changes in eosinophils, i.e., 1) the survival rates, 2) morphological changes and 3) fragmentation of DNA with respect to 2 factors, the steroid concentration and culture time. The steroid or interleukin-5 (IL-5) were added to eosinophils from patients with AD and those from non-AD patients with eosinophilia to compare serial changes in the survival rate. In eosinophils from patients with AD, the survival rate significantly decreased time-dependently and steroid concentration-dependently. Steroid administration significantly inhibited the survival rate of eosinophils from patients with AD compared to the survival rates of monocytes and neutrophils. The nuclei of eosinophils were serially reduced, and disappeared 72 hours after steroid administration. Simultaneously, cell size decreased, although the cell membrane remained intact. Granules developed in the cell membrane. In the steroid-treated group, apoptotic cells appeared earlier than in the untreated group. The number of cells showing apoptosis was increased steroid concentration-dependently. The number of DNA ladders was increased time-dependently and steroid concentration-dependently. In eosinophils derived from patients with AD and those derived from non-AD patients with eosinophilia, treatment with recombinant human (rh) IL-5 prolonged the life-span of cells. However, there were differences in the survival rates. In the presence of rhIL-5, the eosinophils from non-AD patients survived 1.4 times longer than those from AD patients at 24 hours (P < 0.05). In the presence of steroid, the eosinophils from non-AD patients survived twice as long as those from AD patients at 24 hours (P < 0.01). These findings suggest that apoptosis induced by steroids decreases the eosinophil count in vivo in patients with AD. There may be a difference in the incidence of steroid-induced apoptosis between eosinophil cells from patients with AD and those from patients with eosinophilia due to other underlying diseases.
Department of Dermatology, Kinki University School of Medicine, Osaka, Japan.
M
M
Matsukura
H
H
Yamada
T
T
Yudate
T
T
Tezuka
J
J
Chihara
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation; D003876:Dermatitis, Atopic / Q000097:blood / Q000188:drug therapy*; D004804:Eosinophils / Q000187:drug effects* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
D000305:Adrenal Cortex Hormones