Effects of testicular cytokines on proliferation of rat T-leukaemic lymphoblasts in vitro.

A rat acute lymphoblastic leukaemia (ALL) model was used to study the mechanisms involved in the tendency to testicular relapse of ALL in boys. Previous studies have indicated that the infiltration and growth of leukaemic lymphoblasts in the testis are influenced by the same endocrine and paracrine control systems that regulate normal testicular function. In the present study the effects of aqueous extracts of scrotal, abdominal and estrogen-treated postpubertal rat testes on rat-leukaemic lymphoblast proliferation were evaluated. The effects of recombinant cytokines analogous to those observed in the testis on leukaemic cell DNA-synthesis were also evaluated since changes in the levels of these factors have been observed in association with cryptorchidism and low levels of gonadotropins. Transforming growth factor-beta 1 (TGF-beta1), significantly inhibited the proliferation of leukaemic rat lymphoblasts after 24 h of culture, whereas TGF-beta 2, interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6 or combinations of them were inactive. Extracts of estrogen-treated testes and abdominal testes of unilaterally cryptorchid animals inhibited leukaemic T-cell proliferation significantly more than extracts of normal testes. The inhibitory activity in abdominal testes could be neutralized by anti-TGF-beta 1 antibodies. These results suggest that testicular TGF-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 leukaemic cell function in the testis.