In view of the association between essential
fatty acid (EFA) deficiency and human
cystic fibrosis, we have investigated the possible occurrence of
pulmonary disease in rats fed an EFA deficient (EFAD) diet for 40 weeks. In contrast to a few slight spontaneous lesions consisting of pleural membrane
hyperplasia, which were found in the lungs of control rats, a much greater incidence of fibrotic lesions was observed in the lungs of EFAD rats. These pleuropulmonary
fibroses extended from the hyperplastic pleural membrane into the alveoli and were characterized by
collagen deposition and marked macrophage infiltration to the extent that, in some cases, the alveolar septa were completely obstructed by inflammatory exudate. These findings lend indirect support to the contention that EFA deficiency plays a role in the aetiology of
cystic fibrosis, at least with regard to pulmonary lesions. Administration of
methysergide (10 mg/kg/day, p.o.) for a total of 11 weeks, did not alter the incidence of
fibrosis in the lungs of EFAD rats, despite the finding that a man who had developed pleuropulmonary
fibrosis as a result of chronic
methysergide treatment exhibited a relative serum EFA deficiency. While a relative EFA deficiency may be a predisposing factor for the induction of
fibrosis by chronic
methysergide treatment, our data are not sufficient to make a decision upon this hypothesis.