The effect of intracellular antioxidant delivery (catalase) on hydrogen peroxide and proinflammatory cytokine synthesis: a new therapeutic horizon.

UNLABELLED

Reactive oxygen species synthesized by endothelial cells may be responsible for cell damage and altered physiologic function. After endotoxin stimulation, free radicals including H(2)O(2) are produced. We have developed a method of intracellular drug delivery using albumin microcapsules. Catalase would be an excellent compound to alter H(2)O(2) production. However, the large molecular size of catalase limits cellular penetration. Endothelial cells have been previously shown to readily phagocytoze albumin microcapsules.

METHODS

Catalase was added to an albumin solution to form a 10% solution of catalase. Microspheres from 2 to 7 microm in size were formed using a Bucchi spray dryer. Human endothelial cells were incubated with varying concentrations of microencapsulated catalase. The cells were then exposed to Escherichia coli endotoxin to determine if increased intracellular penetration of catalase would inhibit H(2)O(2), nitrate, and cytokine synthesis.

RESULTS

There was a 7.2-fold increase in endothelial intracellular catalase after 48 h incubation. H(2)O(2) was inhibited by 72%, nitrate 96%, TNF 90%, IL1 21%, IL6 42%.

CONCLUSIONS

These results demonstrate that inhibition of H(2)O(2) as a result of increased intracellular delivery of catalase inhibits proinflammatory cytokine synthesis after endotoxin exposure.