EFFECTS OF TESTICULAR CYTOKINES ON PROLIFERATION OF RAT T-LEUKEMIC LYMPHOBLASTS IN-VITRO

A rat acute lymphoMastic leukaemia (ALL) model was used to study the m echanisms involved in the tendency to testicular relapse of ALL in boy s. Previous studies have indicated that the infiltration and growth of leukaemic lymphoblasts in the testis are influenced by the same endoc rine and paracrine control systems that regulate normal testicular fun ction. In the present study the effects of aqueous extracts of scrotal , abdominal and estrogen-treated postpubertal rat testes on rat-leukae mic lymphoblast proliferation were evaluated. The effects of recombina nt cytokines analogous to those observed in the testis on leukaemic ce ll DNA-synthesis were also evaluated since changes in the levels of th ese factors have been observed in association with cryptorchidism and low levels of gonadotropins. Transforming growth factor-beta(1) (TGF-b eta(1)) significantly inhibited the proliferation of leukaemic rat lym phoblasts after 24 h of culture, whereas TGF-beta(2), interleukin-1 al pha (IL-1 alpha), IL-1 beta, IL-6 or combinations of them were inactiv e. Extracts of estrogen-treated testes and abdominal testes of unilate rally cryptorchid animals inhibited leukaemic T-cell proliferation sig nificantly more than extracts of normal testes, The inhibitory activit y in abdominal testes could be neutralized by anti-TGF-beta(1) antibod ies, These results suggest that testicular (T)GF-beta(1) may influence growth of leukaemic lymphoblasts in the testis but also that other as yet unknown, testicular factors are involved in the regulation of leu kaemic cell function in the testis.