Increase of plasma transforming growth factor beta (TGFβ during immunotherapy with IL-2

Pauli Puolakkainen, Dan Twardzik, Jane Ranchalis, Mauro Moroni, John Mandeli, Paolo Alberto Paciucci

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

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 aggregatiori accompanied by rapid secretion of alpha-granule components such as platelet factor 4 (PF4) and beta-thromboglobulin. Platelets coiistitute one of the largest storage forms of TGFβ Preliminary evaluation of this factor in patients receiving IL-2 had indicated that plasma TGFβ activity increased in cancer patients following IL-2 therapy. We report a more detailed study of the quantitation of TCFβ 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 TGFβ 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 TGFP activity appeared to correlate with a decrease of platelet counts, suggesting that the factor may derive from the storage form of TGFβ contained therein.

Original languageEnglish
Pages (from-to)583-589
Number of pages7
JournalCancer Investigation
Volume13
Issue number6
DOIs
StatePublished - 1995

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