Figure 1.

IL-18 drives both the destructive and remodeling processes in the lungs of IL-18 transgenic mice. Novel pathways identified by Kang and coworkers in IL-18 transgenic mice are highlighted with red arrows and lines. Inducible overexpression of IL-18 in the adult murine airway epithelium induces Th1 cytokine expression, leading to increased cytotoxic lymphocytes responses, alveolar septal cell apoptosis, and airspace enlargement. In addition, IL-18 drives Th2 cytokines responses in a Th17-dependent manner, leading to mucus metaplasia, small airway fibrosis, and vascular remodeling with pulmonary hypertension and right ventricular hypertrophy. There is also reciprocal regulation of Th1 and Th17/Th2 cytokine responses and downstream lung pathologies in the lungs of IL-18 transgenic mice.