To understand the role of the proinflammatory
cytokine interleukin-1 (IL-1) in mycobacterial
inflammation,
IL-1 alpha/beta double-knockout (KO) mice were produced. These mice were infected with either Mycobacterium tuberculosis H37Rv by the airborne route using an airborne
infection apparatus, and their capacities to control mycobacterial growth,
granuloma formation,
cytokine, and
nitric oxide (NO) production were examined. The
IL-1 alpha/beta mice developed significantly larger (p < 0.01) granulomatous, but not necrotic, lesions in their lungs than wild-type (WT) mice after
infection with H37Rv. Inflammatory lesions, but not
granulomas, were observed in spleen and liver tissues from both
IL-1 alpha/beta KO and wild-type mice. Granulomatous lesion development in
IL-1 alpha/beta KO mice was not significantly inhibited by treatment with exogenous recombinant
IL-1 alpha/beta. Compared with wild-type mice, splenic IFN-gamma and
IL-12 levels were within the normal range. NO production by cultured alveolar macrophages from
IL-1 alpha/beta KO mice was lower than in wild-type mice but were increased by the addition of recombinant
IL-1 alpha/beta. Our data clearly indicate that
IL-1 is important for the generation of early-phase protective immunity against mycobacterial
infection.