The effect of cortisone on experimental silicosis.

Alterations in cellular and fibrous tissue reaction due to cortisone and A.C.T.H. have been demonstrated in human beings by several workers such as Freeman, Fershing, Wang, and Smith (1950), and by Cavallero, Sala, Amira, and Borasi (1951) in the carbon tetrachloride necrosis of rats' livers. The influence of cortisone on the phagocytic action of the reticulo-endothelial system on carbon particles was studied by Spain, Molomut, and Haber (1950) and on intraperitoneally injected silica particles by Policard and Tuchmann-Duplessis (1951). In both experiments the migration of dustladen phagocytes was retarded. Kennedy, Pare, Pump, Beck, Johnson, Epstein, Venning, and Browne (1951), working in the Department of Professor J. S. L. Browne of Montreal, treated two patients with chronic beryllium granulomatosis and obtained temporary subjective and objective improvement as judged both by respiratory function studies and x-ray films of the lungs. Since chronic berylliosis is characterized by gross fibrosis of the lungs, these workers were encouraged to experiment with the treatment of silicosis by the same means. It is difficult to believe that the densely fibrous nodules which are scattered throughout the lung in silicosis could be influenced to resolve or regress; and this, indeed, was found to be the case by Kennedy and his colleagues, who were unable to observe any change in the x-ray appearance of the lungs of the patient they treated. Nevertheless some relief of his clinical condition was claimed. The cough and sputum disappeared and dyspnoea was relieved. As a result of the reports of these experiments the Cortisone and A.C.T.H. Sub-Committee of the Industrial Pulmonary Diseases Committee of the Medical Research Council asked us and Professor J. Gough of Cardiff to undertake investigations of the effect of cortisone on the production of experimental silicosis in animals. While, as noted above, it seems improbable that the hormone could have any effect on the established lesions of silicosis, it nevertheless appeared possible that the production of fibrous tissue might be retarded by the administration of cortisone, or that there might be some effect on the movement of dust-laden phagocytes into focal areas of accumulation with a consequent slowing up of the fibrotic response. Professor Gough's results have been reported separately (Magarey and Gough, 1952), and an account of our own investigation is given in the prcsent communication. Whereas we have found the predominant effect of cortisone to be on the movement of dustladen phagocytes, Schiller (1951, 1952), Magarey and Gough (1952), and Curran (1952) have demonstrated both an inhibition of fibrosis and an alteration in the mobility of macrophages when quartz dust was injected into the peritoneal cavity.