WHOLE-BODY HYPERTHERMIA INCREASES PLASMA-LEVELS OF TRANSFORMING GROWTH-FACTOR-BETA

The low bone marrow toxicity of high dose alkylating agents when given in combination with whole body hyperthermia (WBH) may be explained in part by the parallel induction of the granulocyte colony stimulating factor. Since transforming growth factor beta (TGF beta) is known to a ct synergistically with colony stimulating factors, we performed studi es of TGF beta expression under WBH in 12 patients with histologically confirmed metastatic sarcoma. Each patient was given ifosfamide, carb oplatin, and etoposide combined with WBH (41.8 degrees C, 1 h). Plasma specimens far determination of TGF beta levels were taken prior to WB H and at different time points after start of WBH. Immunoreactive TGF beta 1 and TGF beta 2 were measured by ELISA. Follow-up revealed a sig nificant increase in TGF beta 1 and TGF beta 2 in 9 of 12 patients, st arting 2 h after begin of WBH and peaking 10 h later. The mean value f or TGF beta 1 prior to therapy was 3.3 ng/ml (range: 0.9-7.3 ng/ml), r ising after 12 h to 5.3 ng/ml (range: 2.8-11,5 ng/ml) (p<0.05). The va lues for TGF beta 2 were 3.1 ng/ml (range: 1.9-4.1 ng/ml) and 3.9 ng/m l (range: 3.2-4.5 ng/ml) (p<0.05), respectively, Both TGF beta 1 and T GF beta 2 had to be activated in vitro by acidification, Initial TGF b eta 1 and TGF beta 2 levels did not differ from those in healthy contr ols. Collectively, our data indicate enhanced TGF beta 1 and TGF beta 2 expression under WBH and support the thesis that TGF beta is a myeol oprotective factor because it stimulates granulopoiesis. The transient growth arrest of very early stem cells by TGF beta may be an addition al factor contributing to the low myelotoxicity of alkylating agents w hen given under WBH.