CARRAGEENAN-INDUCED oedema of the rat foot is used widely as a working model of inflammation in the search for new anti-inflammatory agents,
The test, introduced in 1962 by Winter, Risley and Nuss, appeared to be the basis for the discovery of the new anti-inflammatory drug indomethacin (Winter et al., 1962(Winter et al., , 1963)). Since that time it has been applied with little knowledge of its precise mechanism of action.
The carrageenan model appeared to be almost unique in acute inflammation in that the amines, histamine and 5-hydroxytryptamine (5-HT), were alleged to play no role (Van Arman et al., 1965; Vinegar, Schreiber and Hugo, 1969). This is in marked contrast to many other models of acute inflammation (Spector and Willoughby, 1963, 1965).
There has been some support for the kinin-forming system as a mediator on the basis that oedema is suppressed by antiproteasic agents (Van Arman et al.; Di Rosa and Sorrentino, 1968), and carrageenan is capable of releasing kinin-like substances from plasma substrates (Rothschild, 1966; Di Rosa and Sorrentino, 1968). Di Rosa and Sorrentino (1970) have found that treatment of rats with celIulose sulphate, a kininogen-depleting agent, led to a suppression of the oedema induced by carrageenan that was closely related to the timecourse of kininogen depletion. There remains considerable confusion as to the precise role of kinins in this and other models of inflammation (Spector and Willoughby, 1968).
Carrageenan (Davies, 1963(Davies, , 1965;;Ward and Cochrane, 1965) and cellulose sulphate have an effect upon the complement system (Ecker and Pillemer, 1941 ;Mutsaars and Lison, 1948). Since the complement system (C') appears to act as a trigger mechanism of the acute inflammatory process (Willoughby, Coote and Turk, 1969), it seemed of interest to study the role of C' in carrageenan oedema and its suppression by cellulose sulphate.
Many mediators appear to be involved in the carrageenan oedema including histamine, 5-HT, kinins and the prostaglandins (Willis, 1969a and b). It seemed necessary to reappraise the role of these various mediators in the carrageenan oedema. More general considerations on the pathogenesis of acute inflammation prompted us to extend this study to a comparison of carrageenan oedema and turpentine-induced pleurisy with the aim of obtaining information about the relations between the nature of the irritant and the site of the inflammatory response and the pattern of the pharmacological mediators released.