Effects of 2-aminomethyl-4-t-butyl-6-iodophenol (MK-447) on granulomatous inflammation: lack of correlation with changes in levels of prostaglandin-like material.

MK-447, administered locally to carrageenan-soaked sponges implanted in the backs of rats, either on the day of implantation (day 1) or on days 4-7, exhibited a weak, dose-related inhibition of subsequent granuloma formation. With the later treatment period, prostaglandin (PG)-like material in day 8 exudates was increased at all doses, but with MK-447 treatment on day 1, levels of PG-like material after 24 h were unaffected. Thus, inhibition of granuloma formation was unrelated to local levels of PG-like material. Following treatment with low doses of MK-447 on implantation, mononuclear cell counts in 24 h exudates were reduced. Similar results were obtained with PGE1. Higher doses of MK-447 did not alter monuclear cell counts, but both high and low doses of MK-447 markedly increased polymorphonuclear cell counts in 24-h exudates. The results do not permit the conclusion that the anti-granuloma action of MK-447 is necessarily related to alteration of stable PG level at the inflamed site. Therefore, MK-447 cannot be used unequivocably as a tool to investigate the role of endogenous stable PGs during granulomatous inflammation.