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 the immune system. When administered in vivo, besides inducing unrestricted tumor cytotoxicity, it is also responsible for the secondary release of other lymphokines, such as IL-1, TNF, and marrow growth factors, which may mediate some of the clinical toxicities (as well as therapeutic effects) seen during IL-2 immunotherapy. Among the clinical effects of IL-2, we previously reported thrombocytopenia and IL-2-induced in vitro inhibition of platelet aggregation accompanied by rapid secretion of alpha-granule components such as platelet factor 4 (PF4) and beta-thromboglobulin. Platelets constitute one of the largest storage forms of TGF beta. Preliminary evaluation of this factor in patients receiving IL-2 had indicated that plasma TGF beta activity increased in cancer patients following IL-2 therapy. We report a more detailed study of the quantitation of TGF beta activity in the plasma of 23 cancer patients treated with IL-2 immunotherapy. Of interest, we found that although elevation of the bioactive form of TGF beta occurred in most patients during IL-2 therapy, it was significantly higher in patients with clinical regression of tumor (p = .004). In the first 2 weeks of therapy increase of plasma TGF beta activity appeared to correlate with a decrease of platelet counts, suggesting that the factor may derive from the storage form of TGF beta contained therein.