BERYLLIUM-INDUCED DISTURBANCES OF THE MURINE IMMUNE-SYSTEM REFLECT SOME PHENOMENA OBSERVED IN SARCOIDOSIS

Sarcoidosis is a systemic granulomatous disorder of unknown origin. In respect to clinical and immunological characteristics, it is indistin guishable from berylliosis. As an approach to develop a murine model r eflecting some aspects of sarcoidosis, we attempted to induce beryllio sis in mice by treating inbred F1 mice (C57B16xDBA/2) with 3 mg beryll ium sulfate (BeSO4) per kg body weight intraperitoneally. Either pure BeSO4 or BeSO4 in combination with incomplete Freund's adjuvant was ad ministered. Alternatively, pure BeSO4 was injected 2 days after a sing le application of cyclophosphamide (150 mg/kg). The spleen index, the spontaneous and phorbolmyristate acetate (PMA)-induced radical oxygen intermediates (ROI) released by peritoneal macrophages, and the prolif erative activity of spleen mononuclear cells in response to BeSO4 and concanavalin A (ConA) were evaluated and compared to the corresponding changes observed in sarcoidosis. In all three modes of BeSO4 treatmen t, the spontaneous ROI release by peritoneal macrophages was significa ntly elevated. These elevations were very similar to those observed wi th alveolar macrophages in active sarcoid alveolitis. After BeSO4 trea tment, a small proliferative activity of spleen mononuclear cells in r esponse to BeSO4 could be observed. Further, BeSO4-treated spleen mono nuclear cells exhibited a markedly reduced response to ConA stimulatio n (approximate to 20% of control) which parallels the reduced prolifer ative capacity of sarcoid peripheral blood mononuclear cells (approxim ate to 45% of control). This reduction could be abolished by pretreati ng the mice with cyclophosphamide. BeSO4 treatment in combination with incomplete Freund's adjuvant resulted in a significant increase of sp leen mononuclear cell proliferation (1.9-fold) after in vitro stimulat ion with BeSO4, and prevented the low responsiveness to ConA. All thes e findings were maximal after 2 and vanished after 5 weeks. In conclus ion, BeSO4 treatment of mice yields immunological disturbances which p arallel some immunopathological phenomena of patients with sarcoidosis .