IFNG and major depressive disorder: IFN-γ stimulates the activation of alveolar macrophages and its level is positively associated with the severity of COPD.[40,41] It has also been shown in a clinical study that patients with COPD combined with depression have the highest levels of blood IL-2 and IFN-γ compared to controls.[42] Smoking and other factors are also predisposing factors for COPD.