A permeability factor released from guinea-pig serum by antigen-antibody precipitates.

MANY attempts have been made to identify the mediators of the increased vascular permeability of inflammation. Most of the work has been concerned with the liberation of histamine but, more recently, other substances such as 5-hydroxy-tryptamine, polypeptides and serum globulins have received attention (Spector, 1958). Nearly all the more recent work has dealt with inflammation induced by irritants, burns, releasers of active substances (such as dextran, egg-white, compound 48/80, etc), or with in vitro changes of normal serum, plasma 'or lymph. Little is known about the mediators of allergic inflamimation: it is tacitly assumed by many authors that histamine alone is involved. However, hesitation in accepting the histamine hypothesis stems from the failure of antihistamine drugs to inhibit certain types of allergic response (Brocklehurst, Humphrey and Perry, 1955). This failure is usually explained in terms of Dale's (1948) concept that intrinsically-liberated histamine is less accessible to antagonistic drugs. Rocha e Silva and Rothschild (1955) showed that cutaneous anaphylaxis in rats could still be obtained in animals from which histamine had been depleted by dextran, ovomucoid or compound 48/80. Again, Inderbitzin and Dobric (1959) found that the pattern of changes in histamine content of skin at sites of passive cutaneous anaphylaxis resembled those at adjacent control areas of abdominal skin. They concluded that the skin-histamine released during cutaneous anaphylaxis could not have mediated the resulting inflammation. As an alternative hypothesis, the possibility that allergic inflammation is caused by other substances is equally tenable and should be explored. Allergic reactions result from the interaction of antigen, antibody and body constituents and can take many forms. We have selected for study the acute inflammatory response induced by injecting antigen into the skin of sensitized animals. As a first step we have added antigen-antibody precipitates (Ag/Ab) to serum and studied the ability of the treated serum to cause a rapid and sustained increase in vascular permeability when injected intradermally. In orde:to simplify interpretation of results we have, as far as possible, restricted our