A heightened production of interleukin l/7 (IL-lb) has been reported in microglial-associated amyloid deposits in Alzheimer's disease (AD) brains. These plaques are composed predominantly of pIA4 peptide derived from B-amyloid precursor protein QAPP). We demonstrate that short-term (1 h) IL-l/3-treatment increases /3APPs secretion and concomitantly decreases cell-associated BAPP in human H4 neuroglioma cells. Long-term (5 h) IL-1s treatment did not alter secreted or cell-associated BAPP content. In contrast, the secretion of BIACcontaining epitope was not affected by short-term IL-l/3 stimulation; however, long-term IL-1s treatment decreased the amount of /?/A4-containing epitope secreted from the cells. These results show that IL-l/3 modifies the processing and secretion of j?APP to exacerbate perhaps the neuropathology of AD.