Thymopentin down-regulates both activity and expression of iNOS in blood cells of Sézary syndrome patients

While thymopentin has been used for many years in the experimental treatment of Sézary syndrome (SS), a rare and very aggressive lymphoma, its mechanism of action is still not known. Herein we show that this peptide acts as an inhibitor of isolated iNOS and nNOS isoforms, and reduces iNOS protein/mRNA levels and iNOS activity in blood cells obtained from both healthy donors and SS patients. Similar results were obtained with TPN-2, the Nω-nitro analogue of the Arg-Lys motif present in thymopentin. Additional investigations are necessary to confirm the role and the relative importance of the two mechanisms of iNOS down-regulation in the therapeutic action of these peptides against SS.

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► Thymopentin (TP-5) is used in the experimental treatment of Sézary syndrome (SS).
► Its mechanism of action is still largely unknown.
► TP-5 reduces iNOS protein/mRNA levels and iNOS activity in PBAMCs of SS patients.
► Also TPN-2, a Nω-nitro-Arg-Lys dipeptide, elicits similar effects.
► If the role of iNOS in SS were confirmed, new therapeutic opportunities would arise.