title: Mechanisms of corticosteroid action in immune thrombocytopenic purpura (ITP): experimental studies using ITP-prone mice, (NZW x BXSB) F1.
abstract: 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.
authors.affiliation: Second Department of Internal Medicine, Osaka University Medical School, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Mizutani
authors.forename: T
authors.initials: T
authors.lastname: Furubayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Imai
authors.forename: H
authors.initials: H
authors.lastname: Kashiwagi
authors.forename: S
authors.initials: S
authors.lastname: Honda
authors.forename: H
authors.initials: H
authors.lastname: Take
authors.forename: Y
authors.initials: Y
authors.lastname: Kurata
authors.forename: T
authors.initials: T
authors.lastname: Yonezawa
authors.forename: S
authors.initials: S
authors.lastname: Tarui
authors.forename: S
authors.initials: S
authors.lastname: Ikehara
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D007074:Immunoglobulin G; D008099:Liver / Q000503:physiopathology; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis / Q000187:drug effects; D010976:Platelet Count; D011239:Prednisolone / Q000494:pharmacology* / Q000627:therapeutic use; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D011961:Receptors, Fc / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D011961:Receptors, Fc; D011239:Prednisolone