K. Lieb et al., POTENT INHIBITION OF INTERLEUKIN-6 EXPRESSION IN A HUMAN ASTROCYTOMA CELL-LINE BY TENIDAP, Cell and tissue research, 288(2), 1997, pp. 251-257
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.