A number of compounds have been studied for their ability to antagonize the inflammatory reaction produced by injections of formaldehyde and 5-hydroxytryptamine in the mouse foot. An attempt has been made to elucidate the ways in which certain hydroxybenzoates, pyrazolones, sympathomimetic amines, flavone and flavanone glycosides, local anaesthetics, antihistamines and anti-5-hydroxytryptamine substances produce their anti-inflammatory effect.Several substances occur in damaged tissues which have the ability to increase capillary permeability, the subject having been reviewed by Spector (1958). The presence of such substances does not prove their participation in the mediation of the symptoms observed, and it is difficult to differentiate between the causes and the effects of the process in many types of inflammation. Since Lewis (1927) demonstrated that part of the response of tissues to trauma is mediated by an axon-reflex there has been little work done to discover to what extent this process operates in different types of inflammation. Chambers & Zweifach (1947) have emphasized that little is known about the effect which local changes in blood flow have on the overall inflammatory reaction, and so we have attempted, in the experiments described here, to analyse the anti-inflammatory action of certain drugs which are known to alter blood flow in the skin.
METHODSFormaldehyde-induced inflammation in the mouse foot. The details of the method have been described by Northover & Subramanian (1961a). Adult mice of either sex weighing between 25 and 35 g were used in groups of 6 animals. The animals were pretreated with the test substance, given subcutaneously, one injection 24 hr and another 30 min before the injection of formaldehyde. Where variations of this procedure were used they are indicated in the text. All premedicant injections were made in a dose-volume of 0.1 ml., and all compounds were given either as freshly prepared solutions or suspensions, adjusted, where required, to pH 7 with either sodium hydroxide or hydrochloric acid. Each mouse received 0.1 ml. of an aqueous solution containing 0.5% azovan blue and 0.9% sodium chloride through a lateral tail vein, and then immediately afterwards 0.05 ml. of an aqueous solution containing 4% formaldehyde and 0.9% sodium chloride subcutaneously in the dorsum of the right hind foot. The left hind foot received the same volume of saline alone and acted as a control for the formaldehyde-treated foot. The blue-dye accumulation and the swelling in the test foot compared with the control foot were given subjectively assigned scores of from 0 to 3 by