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Influence of cyclosporin a on growth of an acute T‐cell leukaemia in PVG rats
Author(s) -
Thomson A. W.,
Forrest E. H.,
Smart Louise M.,
Sewell H. F.,
Whiting P. H.,
Davidson R. J. L.
Publication year - 1988
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910410618
Subject(s) - spleen , population , medicine , cd5 , endocrinology , lymph , cyclosporins , immunology , pharmacology , pathology , transplantation , lymphoma , environmental health
Our objective was to examine the effect of cyclosporin A (CsA; 25 or 12.5 mg/kg) on growth of an acute (Roser) T‐cell leukaemia in male PVG rats. The leukaemic blasts were shown (by immiunocytochemical analysis) to have a mature, T‐helpercell phenotype, i.e. , OX‐19 (CD5) ∓ ,W3/25 (CD4) ∓ ,OX44 ∓ MHC‐class I + , OX‐26 + , corresponding to a population comprising 5% of normal rat medullary thymocytes. Animals received 20 × 10 2 viable tumour cells intramuscularly (day 0) and were given either CsA (25 or 12.5 mg/kg) or drug vehicle by gavage from day 0 or day 14, by which latter time leukaemic blasts normally appeared in the circulation. Administration of the higher dose of CsA from day 0 or day 14 significantly delayed the appearance of leukaemic cells in the peripheral circulation, whereas treatment with 12.5 mg/kg was without significant effect. CsA whole blood levels on day 17 were twice as high in leukaemic rats as in normal controls. Leukaemic infiltration of the spleen and the liver was reduced on day 17 after 25 mg/kg CsA, but no such effect was observed in lymph nodes or kidneys. A heterogeneous, host “reactive” cell population, which developed in response to the leukaemia, was inhibited by CsA, indicating that the effect of the drug was probably not mediated by host defence mechanisms. In CsA‐treated leukaemic animals, there was biochemical evidence of synergistic impairment of gtomerular and tubular function.