Microdialysis Sampling for Localized Delivery of Immune Modulators

by Ritter, Miles; Stenken, Julie Ann

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Modulating the wound healing response has become an important topic for implantable sensors. Nitric oxide (NO) has proven to be a key mol. in the suppression of the inflammatory response and its controlled release has been incorporated into vascular and s.c. implanted sensors. How NO modulates the immune response to a foreign object is poorly understood. The long term goal of this work is to use microdialysis sampling probes to deliver NO to a wound site and measure the altered cytokine response. Doing so will help elucidate the role of NO in orchestrating the inflammatory process. Since NO is rapidly oxidized to nitrite and nitrate in biol. systems, quantifying nitrite/nitrate levels correlates with the amt. of nitric oxide released. The Griess reaction was used for total nitrite quantification. Nitrate was reduced to nitrite using nitrate reductase. The Griess reaction assay has a lower detection limit for nitrite of approx. 1 μM. Strategies to optimize the amts. of NO delivered will be presented. In particular, different NONOates will be used that vary in their half-lives. These strategies will be applied in vivo through s.c. implanted microdialysis sampling probes. The affected cytokine profiles will then be collected and analyzed to det. the relationship between nitric oxide levels and cytokine expression. NIH EB 001441 and the Arkansas Biosciences Institute supported this work.