TENFOLD INCREASED INCIDENCE OF SPONTANEOUS MULTIPLE-MYELOMA IN LONG-TERM IMMUNOSUPPRESSED AGING C57BL KALWRIJ MICE/

Citation
J. Radl et al., TENFOLD INCREASED INCIDENCE OF SPONTANEOUS MULTIPLE-MYELOMA IN LONG-TERM IMMUNOSUPPRESSED AGING C57BL KALWRIJ MICE/, Clinical immunology and immunopathology, 79(2), 1996, pp. 155-162
Citations number
20
Categorie Soggetti
Pathology,Immunology
ISSN journal
00901229
Volume
79
Issue
2
Year of publication
1996
Pages
155 - 162
Database
ISI
SICI code
0090-1229(1996)79:2<155:TIIOSM>2.0.ZU;2-V
Abstract
Persons undergoing maintenance immunosuppressive treatment (MIST) were shown to be at increased risk for the development of early malignanci es, often of cells of the immune system. Very little is known about th e late effects of MIST. Some clinical studies indicated an age-related increase in the incidence of plasma-cell disorders, in particular in that of multiple myeloma (MM). In the present study the influence of M IST on the development of monoclonal B-cell proliferative disorders, m onoclonal gammopathies (MG), was studied in an animal model, the C57BL /KaLwRij mouse. This strain is known for its susceptibility to develop with aging MG similar to those in humans. Two widely used treatment p rotocols (azathioprine/prednisolone and Cyclosporin A/prednisolone) we re tested in young and adult mice. Both regiments were shown to increa se 10-fold the incidence of spontaneous multiple myeloma. Unexpectedly , the same high incidence of MM and in addition the development of a l ife-shortening lymphoblastic lymphoma were found in a high frequency i n the control group that received Cremophor EL only, i.e., the solvent of Cyclosporin A. Repeated experiments with another lot of Cremophor showed a 6-fold increased frequency of MM but no lymphoblastic lymphom a. With respect to the life-span and the incidence of hemopoietic neop lasms the least harmful drugs for MIST appeared to be azathioprine/pre dnisolone. The results of the experiments in this C57BL/KaLwRij mouse model ave a warning for increased incidence of MM in susceptible aging individuals and address a question whether Cremophor EL is a safe sol vent for Cyclosporin A. (C) 1996 Academic Press, Inc.