Relation between acute-phase proteins and enhanced bleomycin-induced pulmonary fibrosis in the rat

Intratracheal application of Bleomycin (Bleo) in rats induces interstitial pneumonitis followed by progressive fibrosis. As the presence of high levels of acute-phase proteins (= reactants = APR), especially alpha 2-macroglobulin of the rat (alpha 2M), enhances liver fibrosis, we investigated whether this phenomenon also occurs in rats with Bleo-induced lung fibrosis. The experiments showed that this is the case; lung fibrosis assessed by measuring hydroxyproline, hexosamine, and prolyl-4-hydroxylase was enhanced when just before Bleo application an acute-phase reaction was induced. This effect can be explained by the inhibitory effect of alpha 2M on collagenase. The experiments showed a significant positive correlation between alpha 2M and parameters of fibrosis. This is especially the case in the third week after Bleo application. Bleo itself does not induce a strong acute-phase reaction, notwithstanding the pneumonitis during the first weeks. The increased fibrosis is accompanied by progressive ventilatory disturbances demonstrated by high arterial pCO2 and low pO2. In patients undergoing Bleo treatment, varying levels of APR can be expected, and this could explain the rapid development of fibrosis in individual cases.