In hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D), severe cerebral amyloid angiopathy (CAA) is associated with an inflammatory reaction. Small heat shock proteins (sHsps) are molecular chaperones and association of HspB8 with CAA in HCHWA-D has been observed. The aims of this study were to investigate (1) if other sHsps are associated with the pathological lesions in HCHWA-D brains, (2) if the amyloid-beta protein (A beta) increases production of sHsps in cultured cerebral cells and (3) if sHsps are involved in the cerebral inflammatory processes in both Alzheimer's disease (AD) and HCHWA-D. We conclude that Hsp20, HspB8 and HspB2 are present in CAA in HCHWA-D, and that A beta did not affect cellular sHsps expression in cultured human brain pericytes and astrocytes. In addition, we demonstrated that Hsp20, HspB2 and HspB8 induced interleukin-6 production in cultured pericytes and astrocytes, which could be antagonized by dexamethasone, whereas other sHsps and A beta were inactive, suggesting that sHsps may be among the key mediators of the local inflammatory response associated with HCHWA-D and AD lesions.