Potent inhibition of interleukin-6 expression in a human astrocytoma cell line by tenidap.
Tenidap is a structurally novel antirheumatic agent with anti-inflammatory and analgesic properties. Previous studies have shown that tenidap is able to inhibit the production and action of cytokines such as interleukin-1, interleukin-6 (IL-6) and tumour necrosis factor alpha. However, the mechanisms by which tenidap inhibits cytokine synthesis are not yet known. We investigated in the human astrocytoma cell line U373 whether tenidap inhibits IL-6 synthesis by inhibition of certain signal transduction processes leading to IL-6 synthesis. Cells were stimulated with different substances which have previously been shown to activate protein kinase A or C, reactive oxygen intermediates as well as transcription factors such as nuclear factor kappa B and AP-1 and which all 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 pathway. Since IL-6 has been shown to be involved in the etiopathology of Alzheimer's disease and since the use of nonsteroidal anti-inflammatory drugs appears to be of therapeutical benefit, it is concluded that tenidap should be tested in clinical trials in order to determine whether it may be useful for the treatment of Alzheimer's disease.
Lieb
K
K
Abteilung Psychiatrie und Psychotherapie, Universität Freiburg, Hauptstrasse 5, D-79104 Freiburg, Germany.
Fiebich
B L
BL
Hüll
M
M
Berger
M
M
Bauer
J
J
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001254:Astrocytoma / Q000378:metabolism / Q000473:pathology; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D000078183:Oxindoles; D015290:Second Messenger Systems / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007211:Indoles; D015850:Interleukin-6; D000078183:Oxindoles; C062866:tenidap