Objective: Various studies of emphysema involve long-term exposure of animals to cigarette smoke, focusing on the cell type involved in
the protease/antiprotease imbalance and on extracellular matrix degradation. In emphysema, increased expression of metalloproteinases is
associated with cytokines, and evidence suggests that the matrix metalloproteinase-12 (MMP-12) plays an important role. Our objective was
to investigate tissue inhibitor of metalloproteinase-2 (TIMP-2), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) detection by
immunohistochemical methods in mouse lung. Methods: Male C57BL/6 mice were exposed 3 times a day to the smoke of 3 cigarettes over
a period of 10, 20, 30 or 60 days in an inhalation chamber (groups CS10, CS20, CS30 and CS60, respectively). Controls were exposed to the
same conditions in room air. Results: A progressive increase in the number of alveolar macrophages was observed in the bronchoalveolar
lavage fluid of the exposed mice. The mean linear intercept, an indicator of alveolar destruction, was greater in all exposed groups when
compared to control group. In the CS10, CS20 and CS30 mice, the immunohistochemical index (II) for MMP-12 increased in parallel with
a decrease in II for TIMP-2 in the CS10, CS20 and CS30 mice. The II for the cytokines TNF-α and IL-6 was greater in all exposed groups
than in the control group. Emphysema, with changes in volume density of collagen and elastic fibers, was observed in the CS60 group.
Conclusions:
These findings suggest that cigarette smoke induces emphysema with major participation of TNF-α and IL-6 without participation
of neutrophils.
Keywords: Macrophages, alveolar; Emphysema; Tissue inhibitor of metalloproteinase-2; Interleukin-6.