Recent studies utilizing intraperitoneal (i.p.) administration of NSAIDs to rabbits after surgical injury to the parietal peritoneum demonstrated macrophage involvement. NSAIDs are known to inhibit the metabolism of arachidonic acid to prostaglandins, which in turn modulate a variety of macrophage functions. Studies presented here examine the effects of tolmetin administration on peritoneal resident and post-surgical leukocyte functions, such as phagocytosis, the release of superoxide anion and tumoricidal activity. Rats, either non-surgical or following peritoneal surgery, were injected i.p. with tolmetin. At various times after treatment, the rats were sacrificed and peritoneal cells collected by lavage. The phagocytic capability of peritoneal leukocytes was transiently decreased 5-7 days after the administration of tolmetin to normal animals. However, administration of tolmetin during surgery extended the lenght of time that phagocytic capability was enhanced. In non-surgical controls, there was an elevation in superoxide anion release and tumoricidal activity 24 h after tolmetin administration. Superoxide anion release was suppressed at days 5 and 7 after treatment, but returned to control levels by day 14. Intraoperative administration of tolmetin significantly elevated superoxide anion release at days 3 and 5, phagocytosis at days 7 and 14 and tumoricidal activity at day 3. These studies suggest that compounds which suppress prostaglandin synthesis can modulate the function of resident and post-surgical peritoneal cells.
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