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Mechanisms of corticosteroid action in immune thrombocytopenic purpura
(ITP): experimental studies using ITP-prone mice, (NZW x BXSB) F1
H Mizutani, T Furubayashi, Y Imai, H Kashiwagi, S Honda, H Take, Y Kurata, T Yonezawa, S Tarui and S Ikehara
Second Department of Internal Medicine, Osaka University Medical School,
Japan.
To determine the mechanism by which platelet counts increase after
corticosteroid therapy for human immune thrombocytopenic purpura (ITP), we
studied the platelet kinetics using prednisolone (PDN)-treated ITP- prone
mice, (NZW x BXSB) F1 (W/B F1). An increase in platelet counts was observed
in W/B F1 mice (n = 10, mean +/- SD, 1,202 +/- 202 x 10(3)/microL) 4 weeks
after treatment with PDN (2 mg/kg/d); no increase occurred in nontreated
W/B F1 mice (n = 5,651 +/- 126, P less than .005). Prolonged platelet
life-spans (PLSs) were observed in treated W/B F1 mice (1.29 +/- 0.40
days), but not in nontreated controls (0.60 +/- 0.24 days, P less than
.01). No increase in platelet production (platelet turnover) was found in
PDN-treated W/B F1 mice, but significant decreases in platelet-associated
antibodies (PAAs) and platelet-bindable serum antibodies (PBAs) were noted.
Studies on organ localization of radiolabeled platelets showed that hepatic
uptake significantly decreased in the treated W/B F1 mice, but not in
nontreated W/B F1 mice. To elucidate the effect of PDN on the reticulo-
endothelial phagocytic activity in W/B F1 mice, we studied in vivo
clearance of IgG-sensitized, 51Cr-labeled autologous erythrocytes. W/B F1
mice treated with PDN showed a marked impairment of their ability to clear
these cells, although PDN had little effect on the number of splenic or
hepatic macrophage Fc gamma receptors. These results and our previous
findings of splenectomy suggest that PDN improves platelet counts not only
by suppressing systemic reticulo-endothelial phagocytic function but also
by reducing antibody production.
Volume 79,
Issue 4,
pp. 942-947,
02/15/1992
Copyright © 1992 by The American Society of Hematology
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