INCREASE OF PLASMA TRANSFORMING GROWTH-FACTOR-BETA (TGF-BETA) DURING IMMUNOTHERAPY WITH IL-2

Interleukin-2 (IL-2) is a lymphokine with pleiotropic activities on th e immune system. When administered in vivo, besides inducing unrestric ted tumor cytotoxicity, it is also responsible for the secondary relea se of other lymphokines, such as IL-1, TNF, and marrow growth factors, which may mediate some of the clinical toxicities (as well as therape utic effects) seen during IL-2 immunotherapy. Among the clinical effec ts of IL-2, we previously reported thrombocytopenia and IL-2-induced i n vitro inhibition of platelet aggregation accompanied by rapid secret ion of alpha-granule components such as platelet factor 4 (PF4) and be ta-thromboglobulin. Platelets constitute one of the largest storage fo rms of TCF beta. Preliminary evaluation of this factor in patients rec eiving IL-2 had indicated that plasma TGF beta activity increased in c ancer patients following IL-2 therapy. We report a more detailed study of the quantitation of TGF beta activity in the plasma of 23 cancer p atients treated with IL-2 immunotherapy. Of interest, we found that al though elevation of the bioactive form of TGF beta occurred in most pa tients during IL-2 therapy, it was significantly higher in patients wi th clinical regression of tumor (p =.004). in the first 2 weeks of the rapy increase of plasma TGF beta activity appeared to correlate with a decrease of platelet counts, suggesting that the factor may derive fr om the storage form of TGF beta contained therein.