POTENT INHIBITION OF INTERLEUKIN-6 EXPRESSION IN A HUMAN ASTROCYTOMA CELL-LINE BY TENIDAP

Tenidap is a structurally novel antirheumatic agent with anti-inflamma tory and analgesic properties. Previous studies have shown that tenida p is able to inhibit the production and action of cytokines such as in terleukin-1, interleukin-6 (IL-6) and tumour necrosis factor a. Howeve r, the mechanisms by which tenidap inhibits cytokine synthesis are not yet known. We investigated in the human astrocytoma cell line U373 wh ether tenidap inhibits IL-6 synthesis by inhibition of certain signal transduction processes leading to IL-6 synthesis. Cells were stimulate d with different substances which have previously been shown to activa te protein kinase A or C, reactive oxygen intermediates as well as tra nscription factors such as nuclear factor kappa B and AP-1 and which a ll result in IL-6 synthesis. Tenidap was a very potent inhibitor of IL -6 synthesis independent of the stimuli used, suggesting an inhibitory mechanism other than inhibition of a certain signal transduction path way. Since IL-6 has been shown to be involved in the etiopathology of Alzheimer's disease and since the use of nonsteroidal anti-inflammator y drugs appears to be of therapeutical benefit, it is concluded that t enidap should be tested in clinical trials in order to determine wheth er it may be useful for the treatment of Alzheimer's disease.