Although the involvement of T helper (Th1) cells is central to protection against intracellular bacteria, including Mycobacterium tuberculosis, the involvement of Th2 cells, characterized by potent
interleukin (IL)-4 secretion in mycobacterial
infection is still unclear. In order to clarify the role of
IL-4 in murine
tuberculosis, IL-4-deficient mutant mice,
IL-4 knockout (IL-4 KO) mice, were utilized. The mice were infected with H37Rv, Kurono or BCG Pasteur via an airborne
infection route by placing them in the exposure chamber of a Middlebrook airborne
infection apparatus. Their capacity to control mycobacterial growth,
granuloma formation,
cytokine secretion, and
nitric oxide (NO) production were examined. These mice developed large
granulomas, but not necrotic lesions in the lungs, liver or spleen (P<0.05). This was consistent with a significant increase in lung colony-forming units (CFU). Compared with levels in wild-type mice, upon stimulation with mycobacteria, splenic
IL-10 levels were low and
IL-6 levels were intermediate, but
interferon (IFN)-gamma and
IL-12 levels were significantly higher.
IL-18 levels were within the normal range. The level of NO production by alveolar macrophages of the
IL-4 KO mice was similar to that of the wild-type mice. Granulomatous lesion development by
IL-4 KO mice was inhibited significantly by treatment with exogenous recombinant
IL-4. These findings were not specific to the
IL-4 KO mice used. Our data show that
IL-4 may play a protective role in defense against mycobacteria, although IFN-gamma and
TNF-alpha play major roles in it. Our data do not rule out an IFN-gamma-independent function of
IL-4 in controlling
tuberculosis.