In situ expression of cytokines and cellular phenotypes in the lungs of mice with slowly progressive primary tuberculosis

The cellular phenotypes and the expression of cytokines were studied in the lungs of mice, using immunohistochemistry, during different phases of slow ly progressive primary murine tuberculosis infection. During the first phas e the small focal lesions in healthy mice contained predominantly interleuk in-2 (IL-2)-expressing cells. A small number of tumour necrosis factor-alph a (TNF-alpha)-, monocyte chemoattractant protein-1 (MCP-1)- and IL-10-expre ssing cells were also present. IL-4-expressing cells were not detected. Dur ing the second phase the mice became unwell, but the bacterial counts and t he size of focal lesions stabilized. IL-4-expressing cells appeared. The IL -10-, TNF-alpha- and MCP-1-expressing cells increased in number. On progres sion to phase three, the mice became seriously unwell and died rapidly. The inflammation spread to approximate to 80% of the lung parenchyma. There wa s a marked increase in the number of IL-10-expressing cells. Expression of other cytokines was similar to that observed in the second phase. In the le sions, 3-6% of the macrophages (M phi) containing mycobacterial antigens ex pressed high levels of IL-10 and TNF-alpha. The absolute numbers of CD3-, C D4- and CD11b-expressing cells in the lesions increased with the progressio n of infection. The numbers of CD8(+) cells were reduced in the last phase of infection. The kinetics of T-lymphocyte subsets and the pattern of cytok ine expression changed with the type and degree of tissue injury. The small number of M phi with a heavy load of mycobacterial antigens may be the cau se of this disturbance in cytokine balance, thus leading to progression of inflammation.