The study in mouse model of BCG-induced granulomatous inflammation showed that early pulmonary fibrosis (day 3-30 postinfection) in tuberculous inflammation was primarily determined by increased number of fibroblasts in the lung interstitium and granulomas and enhanced fibroplastic activity. Fibroplastic processes are initiated via an increase in secretory activity of activated granuloma macrophages caused by the persistence of the pathogen in the cells of the mononuclear phagocytic system. The dynamics of hydroxyproline concentration under these conditions is determined by changes in the number and differentiation degree of fibroblasts in granulomas and lung interstitium at various stages of tuberculous inflammation.

Generalized BCG-induced granulomatous was simulated in BALB/c male mice. The number of tuberculous granulomas in the liver and their size as well as the number of hepatocytes showing vacuolar degeneration increased from day 3 to 180 postinfection. Necrotic changes in hepatocytes were most pronounced at the acute phase of inflammation (days 3 to 30). Proliferative processes in the liver parenchyma in the experimental group were less marked than in the control. Increased content of collagen fibers in the liver was determined by excessive collagen synthesis in necrotic areas as well as increased amount of granulomas and fibroblasts. Enhanced proliferative and fibroplastic activity of fibroblasts in granulomas and liver parenchyma was evidently determined by activated granuloma macrophages. These shifts determined changes in the liver content of hydroxyproline during the acute and chronic periods of the disease.

In generalized BCG granulomatosis, fibrosis starts early (on day 3) and not only around the granulomas, but also in the organs. The severity of organ fibrosis is apparently determined by the concentration of granulomas, in particular their macrophages inducing proliferation of fibroblasts in organs and granulomas as well as activation of fibrogenesis. On day 30 after infection, the degree of fibrosis in the lungs was by 6 times higher than in the liver. The increase in hydroxyproline concentration in organs in early period of infection was determined by acute stress, while on day 30 it resulted from its enhanced synthesis by granuloma fibroblasts and resident fibroblasts in organs.