Interleukin-6-associated inflammatory processes in Alzheimer's disease: new therapeutic options.
The cytokine interleukin-6 is consistently detected in the brains of Alzheimer's disease patients but not in the brains of nondemented elderly persons. Until recently it was unclear whether an interleukin-6-associated inflammatory mechanism is an early or late event in the pathological cascade of Alzheimer's disease. We investigated whether interleukin-6 could be detected in plaques of Alzheimer's disease patients prior to the onset of neuritic degeneration. We found interleukin-6 mostly in plaques where neuritic pathology has not yet developed. This indicates that the appearance of interleukin-6 may precede neuritic changes and is not just a consequence of neuritic degeneration. Therefore, one may hypothesize that activation of inflammatory mechanisms may cause neuritic degeneration in plaques. A suppression of interleukin-6 synthesis could, therefore, be of therapeutic value. Upon screening a number of substances, we found that a small number of nonsteroidal antiinflammatory drugs, including tenidap, were able to inhibit interleukin-6 synthesis in cultured human astrocytoma cells. These substances may be therapeutically useful in Alzheimer's disease and should be evaluated in clinical studies.
Department of Psychiatry, Freiburg University Medical School, Germany.
M
M
Hüll
B L
BL
Fiebich
K
K
Lieb
S
S
Strauss
S S
SS
Berger
B
B
Volk
J
J
Bauer
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D001254:Astrocytoma / Q000378:metabolism; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry / Q000502:physiology; D001932:Brain Neoplasms / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D009410:Nerve Degeneration / Q000502:physiology; D016501:Neurites / Q000502:physiology; D016874:Neurofibrillary Tangles / Q000473:pathology; D014407:Tumor Cells, Cultured
D015850:Interleukin-6