SYSTEMIC ADMINISTRATION OF IL-2 AND IFN-ALPHA ALTERS HEPATIC DRUG METABOLISM

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In this project, we have been studying the effect of IL-2 and IFN-alpha on hexobarbital induced sleep time of C57BL/6 mice as a function of liver drug metabolizing capability. We have also studied drug metabolizing enzymes, e.g. , ethylmorphine demethylase, epoxide hydrolase, benzphetamine demethylase and benzopyrene monoxygenase. These studies indicate that IL-2 alone prolongs hexobarbital induced sleep time of mice in a dose dependent manner. IFN-alpha caused only marginal prolongation of sleeping time but, when administered in combination with IL-2, a significant increase in sleep time was observed compared to that caused by IL-2 alone and IFN-alpha alone These studies indicate that administration of these immunomodulators may modify patient capability to metabolize normally metabolized drugs. We have further observed that pretreatment irradiation of hosts abrogates the toxic effects of these cytokines implicating radiosensitive cells. The experiment performed in nude mice further indicate that T lymphocytes play a predominant role in such toxicity.