A model of pulmonary granulomata induced by beryllium sulfate in the rat

In humans beryllium is known to cause pulmonary granulomata which are histologically indistinguishable from sarcoidosis. There is some evidence in man that beryllium-induced pulmonary granulomata are immunologically mediated. We set out to develop an animal model to study the immunopathogenesis of beryllium-induced granulomatous lung disease. Beryllium sulfate (BeSO4) was injected intratracheally (i.t.) into F344 rats previously immunized to BeSO4. This results in well-formed, sarcoid-like lung granulomata at 6 weeks post BeSO4. There was a conspicuous presence at 4 weeks post BeSO4 of numerous, perivascularly located Langhans' giant cells which preceded the development of well-formed granulomas at 6 weeks. Rats were sacrificed at 4, 6, 8 and 12 weeks after i.t. BeSO4. At the time of sacrifice bronchoalveolar lavage (BAL) was performed; B and T (W3/25+ helper 0X8+ suppressor/cytotoxic) lymphocyte populations were quantitated and compared to lymphocyte populations obtained from lung tissue. Both B and T cells were significantly elevated in lung tissue post BeSO4. At 4 weeks when granulomata were just developing, a W3/25+ to 0X8+ ratio of 20:1 in lavage and 2:1 in lung tissue was seen. At 6 weeks when granulomata were well-formed there was a predominance of W3/25+ cells in lavage but not in lung tissue. At 8 and 12 weeks, when the granulomata were regressing, lavage fluid still contained a W3/25+ predominance in contrast to lung tissue which contained a predominance of 0X8+ cells.(ABSTRACT TRUNCATED AT 250 WORDS)