TNF and Cognitive impairment: However, the impairment of phagocytosis marks the transition from early to late apoptotic phase, resulting in increased permeability (Poon et al. 2009).The cells exposed to the later phase of apoptosis release proinflammatory cytokines like IL-6 and TNF-α which may be responsible for the neuroinflammatory properties of methotrexate and 5-fluorouracil that can be attributed to their cognitive impairment effects shown in different preclinical and clinical studies (John et al. 2021, 2022).