The production profile of interleukin 1 (IL-1) from mouse peritoneal macrophages (Mø) was determined following their incubation with poly( dl-lactic acid) (PDLLA) granules containing ovalbumin (OVA). Upon incubation, Mø produced IL-1 at a significantly high rate compared with those incubated with OVA in the free form or OVA-free granules. A simple mixture of empty granules and free OVA exhibited the same level of IL-1 production as induced by free OVA alone. IL-1 production by the granules with a fixed OVA loading increased with an increase in their amount added to Mø. When incubated with a fixed amount of granules containing OVA of different loadings, Mø produced more IL-1 with an increase in the total OVA amount, but the IL-1 production decreased at OVA loadings higher than 10%. The presence of free OVA enhanced IL-1 production with the increased addition of empty granules, but the level induced by OVA loaded in granules was higher than that by mixtures of free OVA and empty granules, when compared at a similar OVA dose, irrespective of the absolute amount of PDLLA added. These findings indicate that the sustained release of OVA from the granules is critical to enhance the OVA-induced IL-1 production, in contrast to the OVA release accompanying a large initial burst, which reduced IL-1 production. It was concluded that the direct contact of PDLLA granules with Mø and the subsequent sustained release of OVA around Mø effectively activated Mø, resulting in enhanced IL-1 production.
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