Serum angiotensin-converting-enzyme in rabbits with and without pulmonary granulomatosis. Granulomatosis induced with complete-Freund's-adjuvant or BCG.

An animal model with pulmonary, non-caseating, granulomatosis was successfully reproduced in rabbits utilizing intravenous injections of complete-Freund's-adjuvant (CFA) or BCG. Granuloma formation from CFA injections was limited to the lungs, but BCG injections caused systemic granulomatosis (lung, liver and spleen) irrespective of whether the BCG was dissolved in saline or in incomplete-Freund's-adjuvant (IFA). Serum angiotensin-converting-enzyme (ACE) levels began to rise approximately 15 days following the intravenous injection of CFA, but similar rises following the injection of IFA without granuloma formation suggest that the ACE rise was not necessarily reflective of granuloma formation in rabbits. BCG in saline caused no rise in serum ACE, but when suspended in IFA the ACE rise was comparable to that resulting from IFA alone. However, the ACE level of broncho-alveolar-lavage cells obtained from rabbits 21 days post-injection of CFA was 7-fold higher than that of lavaged cells obtained 42 days post injection, correlating with an acute alveolitis occurring early during granuloma formation. These studies confirm the usefulness of intravenous injections of CFA or BCG for inducing a granulomatous state, but show that the assay of serum ACE is not useful for reflecting the granulomatous state in rabbits. In addition, serum ACE levels are 2-5 X higher in rabbits than in humans and tend to fluctuate spontaneously following delivery of the animals to the laboratory.