Increased T cell cytotoxicity by Betathine (TM)-induced upregulation of TNF alpha

Betathine(TM) (BT) is a low molecular weight disulfide that has previously been shown to exhibit in vivo antitumor activity in murine myeloma and mela noma models. We have shown that BT treatment of both human T cells and mono cytes is associated with an increase in surface tumor necrosis alpha (TNF a lpha) expression. Further, in T cells and monocytes that have been stimulat ed with PMA and ionomycin, the addition of BT results in a dose and time de pendent increase in the percentage of high TNF alpha-expressing cells. Unli ke TNF alpha upregulation produced by the commonly used thiol antioxidant N -acetyl-L-cysteine (NAC), the BT-induced increase in TNF alpha is observed consistently in different donors. This increase in surface TNF alpha is ass ociated with elevated levels of TNF alpha, mRNA. In addition, expression of TNF alpha receptor I is also significantly enhanced by BT treatment. The u pregulation of surface TNF alpha by BT has functional consequences, in that , PT-treated T cells exhibit enhanced cytotoxic activity. Thus, increased T NF alpha expression may be one mechanism responsible for the antineoplastic activity of BT. (C) 2000 International Society for Immunopharmacology. Pub lished by Elsevier Science Ltd. All rights reserved.