On the mechanism through which obstructive jaundice influences inflammatory processes.

A variety of experiments on animals had shown that the antiphlogistic effect of systemic stress is largely non-specific, in that it can be elicited by various agents and is effective in suppressing inflammation in various sites. For instance, systemic stress induced by diverse procedures, if it is sufficiently severe to elicit an intense general adaptation syndrome, markedly inhibits the so-called "histamine appendicitis" (Selye, 1936, 1937a), different varieties of acute inflammatory lung-oedema (Selye, 1938a, 1938b), and the anaphylactoid inflammation caused by egg-white in the rat (Selye, 1937b; Leger, 1948). Subsequently, it became evident that-at least under certain "conditioning" circumstancessystemic stress can also facilitate the production of inflammatory lesions (e.g. nephritis and myocarditis after exposure to cold). The adrenals were suspected of playing an important part both in the inhibition and in the enhancement of inflammatory phenomena by stress, since they were found to be greatly enlarged during the general adaptation syndrome, and since both the antiand the prophlogistic effects of stress could be prevented by adrenalectomy (Selye, 1937b, 1946). When pure corticoids became available, it was noted that some, the "mineralo-corticoids", are also "prophlogistic corticoids" (e.g. desoxycorticosterone) in that they stimulate, while others, the "gluco-corticoids", are also "antiphlogistic corticoids" (e.g. cortisone or cortisol) in that they inhibit inflammation (Selye, 1949; Selye and Pentz, 1943). However, the effects of endogenous cortical hormones upon inflammation are not solely dependent upon the rate of their production; the activity of these corticoids can be considerably modified by a variety of "conditioning factors" (Engel, 1953; Selye, 1954). The liver had long been suspected of playing an important role in this connexion. In the course of studies on the mechanism of this conditioning, we came to examine the influence of various experimentally induced hepatic injuries (partial hepatectomy, ligature of the common bileduct) upon the actions of desoxycorticosterone, the first corticoid to be made available by synthesis (Selye, 1941, 1943; Selye and Stone, 1944). It was found that the effectiveness of this and many allied steroids can be strikingly enhanced by partial removal of hepatic tissue. Independently, clinical experience had shown that, in patients with hepatic damage, inflammatory processes, and, in particular, rheumatoid lesions, tend to regress. The question arose whether this beneficial effect is merely due to an increased endogenous production of ACTH and of antiphlogistic corticoids -due to the systemic stress caused by the hepatic damage-or whether the liver is also more specifically involved in conditioning the efficacy of the corticoids after they are discharged into the blood. We were especially interested in clarifying this point, because of its practical importance. At present one of the greatest handicaps in the clinical use of antiphlogistic corticoids (e.g. for the treatment of rheumatoid and allied inflammatory conditions) is that often they are effective only at comparatively high dose-levels, at which unpleasant side-effects are rather common. A better understanding of the mechanism through which inflamed tissue can be "conditioned" or sensitized to antiphlogistic corticoids might show us how to obtain optimal effects with relatively low and safe doses (Selye, 1952; Selye and Horava, 1953). The purpose of this communication is to report upon experiments in which the common bile-duct was severed in adrenalectomized rats which were maintained either with an antiphlogistic (cortisone) or a prophlogistic (desoxycorticosterone) hormone. A standardized, objectively-measurable inflammatory focus was then produced as an indicator of