BACKGROUND: Interleukin-4 (IL-4) is a cytokine of Th2 response and plays a role as a reducer or silencer of Th1 work. It is more related to allergic processes, with consequent loss of control of the disease (i.e., tuberculosis). Interferon gamma (IFN-γ) is a Type II interferon that inhibits Th2 immune response and inducts Th1 immune response to inhibit tuberculous and viral replication, and any immunostimulatory and immunomodulatory effects. Dark specks (DS) are in the background of eosinophilic granular material seen in aspirations of tuberculous lymphadenitis stained with May–Grunwald Giemsa (MGG). A lesion with DS festers and the disease worsens. AIM: This study determines whether the expression of IL-4 is associated with disease severity and compares incidences of expression of IL-4 and IFN-γ in DS lesions. MATERIALS AND METHODS: This study includes 100 diagnostic cases of tuberculous lymphadenitis, which were not successfully treated with common antibiotics, but responded to anti-tuberculous drugs (ex juvantibus diagnosis). Out of the 100 cases, 59 cases were with DS and 41 cases were without DS. Out of the 59 cases with DS, 49 cases were IL-4 positive (+) and 10 cases IL-4 negative (–). Of the 41 cases without DS, 10 cases were IL-4 (+) and 31 cases were IL-4 (–). Out of the 59 cases of DS, there were 31 cases with expressions of IL-4 (+) and IFN-γ (–); zero case with IL-4 (–) and IFN-γ (+); 18 cases with IL-4 (+) and IFN-γ (+); and 10 cases with IL-4 (–) and IFN-γ (–). Antigen expressions were determined using rabbit polyclonal to IL-4 (IL-4, ab9622) and rabbit polyclonal to IFN-γ (IFN-γ, ab9657), Abcam. Statistical evaluations were performed using the Chi-square test and Fisher’s exact test. Any p < 0.05 was statistically significant. RESULTS: Expression of IL-4 significantly associated with disease severity, compared to IFN-γ expression (p < 0.05). In lesions with DS, IL-4 is more frequently expressed compared with IFN-γ. CONCLUSION: IL-4 can be a beneficial indicator of the severity of tuberculous lymphadenitis.