iNOS, an enzyme involved in the macrophage inflammatory response and upregulated by hypoxia or proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), or interferon-γ (IFN-γ), plays a crucial role in the development of tobacco smoke–induced emphysema and PH in mice (61). Here, TNF is linked to pulmonary emphysema.