CELLULAR IMMUNOLOGY 93, 189- 198 ( 1985) The Effect of Hydrocortisone and Cyclosporin A on Bacillus Calmette-G&in Epithelioid Cell Granulomas SUNIL K. GUPTA, JILL CURTIS, AND JOHN L. TURK Department of Pathology, The Royal College of Surgeons of England, 35-43 Lincoln’s Inn Fields, London WC2A 3PN, England Received December 6, 1984; accepted January 26, 1985 The injection of bacillus Calmette-G&in (BCG) intradermally into the ear of guinea pigs leads to the formation in the draining lymph node of granulomas containing epithelioid cells with rough endoplasmic reticulum (RER) and an absence of phagocytosed material. BCG granulomas in hydrocortisone- or cyclosporin A (CsA)-treated animals contain mononuclear phagocytes with no RER. In CsA-treated animals, these cells contain fragments of phagocytosed organisms. CsA was given at two doses, 25 mg/kg orally and 50 mg/kg ip. The higher dose completely suppressed the delayed hypersensitivity (DH) responseto purified protein derivative (PPD) but the lower dose did not affect the level of the DH response, but had a profound effect on epithelioid cell formation. The role of lymphokines in the maturation of the monocyte/ macrophage to epithelioid cells is discussed. 0 1985 Academic Press. Inc. INTRODUCTION Cells of the mononuclear phagocyte seriesplay an important role in resistance to infection with intracellular parasites. The mononuclear phagocyte series is made up of a wide variety of cells performing a variety of complex functions (1). Epithelioid cells in the granulomas of chronic infections are among the cells considered to belong to this series. The presence of epithelioid cells is a particular feature of granulomas associated with immunologic reactivity. One of the most extensively studied granulomas has been that induced by bacillus Calmette-G&in (BCG) vaccine. In these studies emphasis has been placed on dermal and pulmonary granulomas (2-4). Narayanan et al. (5, 6) showed that the intradermal injection of live BCG Pasteur in the dorsum of the ear of the guinea pig produced typical epithelioid cell granulomas in the draining (postauricular) lymph nodes which showed maximum infiltration at 2 weeks. Ultrastructurally, epithelioid cells present in the BCG granulomas were characterized by a large nucleus with a prominent nucleolus, a paucity of cytoplasmic organelles, the presence of a rough endoplasmic reticulum, and no phagocytosed material. The presence of epithelioid cells in granulomas has been shown to be associated with strong cell-mediated immunity (7, 8). Studies in thymectomized mice have shown that the development of delayed hypersensitivity is not essentialfor granuloma formation, but can augment and accelerate the epithelioid cell granulomatous response (9, 10). Mice infected with Mycobacterium leprae develop an effective 189 0008-8749185$3.00 Copyright 0 1985 by Academic Press, Inc. All rights of reproduction in any form resened.