EFFECT OF VARIOUS NUCLEIC ACID AND PROTEIN SYNTHESIS INHIBITORS ON ANAPHYLACTOID INFLAMMATION IN RATS

The effects of several nucleic acid and protein synthesis inhibitors (NAPSI) on dextran anaphylactoid inflammation, and on foot oedema evoked by compound 48/80 and serotonin (5-HT) were investigated in rats. Pretreatment with actinomycin D, mannomustine, 6-mercaptopurine (6-MP), emetine and chloramphenicol inhibited the inflammatory response induced by dextran and compound 48/80, but did not influence the response to 5-HT. A marked anit-inflammatory action of actinomycin D, mannomustine and emetine was present within 30 hr of giving the first dose, while the anti-inflammatory effect of 6-MP and chloramphenicol developed only after 12 days pretreatment. Intrapedal injection of an extract (0.1 ml) prepared freshly from the shock-organ of normal rats significantly antagonized the anti-inflammatory effect of the treatment with NAPSI in acute experiments. The authors suggest that pretreatment with NAPSI interferes with the de novo synthesis of the enzyme(s) which play a role in the release of those substances mediating the inflammatory reaction. The anti-inflammatory activity of these drugs can be attributed to the decreased level of enzyme(s) participating in the early vascular phase of the acute inflammation. © 1969.