Attenuation of bleomycin-induced pneumopathy in mice by monoclonal antibody to interleukin-12

We previously demonstrated essential roles of the Fas-Fas ligand (FasL) pat hway in bleomycin-induced pneumopathy in mice. T lymphocytes and natural ki ller cells express FasL on activation and use it as a cytotoxic effector mo lecule. Because interleukin (IL)-12 is known to play a critical role in cel l-mediated immunity, we investigated whether anti-IL-12 antibody treatment suppresses the development of this model. The anti-IL-12 antibody treatment decreased the number of apoptotic cells and the degree of inflammation and fibrosis in lung tissue. The results of RT-PCR showed that IL-12p40, IL-12 receptor (R) beta2, interferon-gamma, tumor necrosis factor-alpha and FasL mRNAs were upregulated after bleomycin instillation. The upregulation of F asL, IL-12R beta2, and tumor necrosis factor-alpha mRNA expression in lung tissue was suppressed by anti-IL-12 antibody treatment. The results of enzy me-linked immunosorbent assay showed that the levels of IL-12p40, but not o f IL-12p70, were increased in lung tissue after bleomycin instillation. Alt hough the increase in IL-12R beta2 mRNA levels suggests that the T helper t ype 1 cell response may participate in lung injury, the increase in IL-12p4 0 supports T helper type 2 cell predominance in the fibrotic process of thi s model. The administration of anti-IL-12 antibody could be a novel therapy against lung injury and pulmonary fibrosis.