Permeability factors in lymph draining inflamed tissues: effect of anti-inflammatory drugs

1. Inflammatory responses were induced by the injection of carrageenin into the rat paw and lymph was collected by cannulation of the thoracic duct. Cell-free lymph samples were intracutaneously injected into a second group of rats to measure vascular permeability activity by local exudation of Evans blue. 2. The vascular permeability activity in lymph samples draining inflamed tissue was consistently higher than in lymph from normal controls. Activity increased with the development of inflammation, attaining maximum values 2 to 2.5 h after the injection of carrageenin. 3. The activity was reduced by pretreatment of lymph donors with indomethacin or soybean trypsin inhibitor. Pretreatment of the animals used to measure vascular permeability activity with diphenhydramine or methysergide attenuated their responses to the permeability factors present in lymph. Thus prostaglandins, kinins, vasoactive amines or their generating systems may have contributed to the total activity detected. 4. Pretreatment of lymph donors with corticosterone or glucagon, whose anti-inflammatory action is mediated by the release of endogenous corticosteroids, did not alter the amount of activity in lymph. 5. These data suggest that the formation of the permeability factors present in lymph draining inflamed tissue was not affected by corticosteroids. We conclude that corticosteroids do not exert their anti-inflammatory activity at this level.