*2.2.2 Biological roles of TNF-α*

Several biological functions are ascribed to the TNF-α, and for this reason, the mechanism of action is somewhat complex. Because this protein confers resistance to certain types of infections and in parallel causes pathological complications, it carries out contradictory roles. This may be connected to the varied signaling pathways that are activated. TNF-α modulates several therapeutic roles within the body, such as immunostimulation, resistance to infection agents, resistance to tumors, sleep regulation, and embryonic development [17]. On the other hand, parasitic, bacterial, and viral infections become more pathogenic or fatal due to TNF circulation. The major role of TNF is explicated as mediator in resistance against infections. Moreover, it was postulated that TNF plays a pathological role in several autoimmune diseases such as graft versus host rejection or rheumatoid arthritis. In addition, TNF exhibits antimalignant cell cytotoxicity in association with interferon. High concentrations of TNF-α are toxic to the host. The enhancement in the therapeutic index by decreasing toxicity or by increasing effectiveness is indeed needed. This may be possible through the mutations that reduce systemic cytotoxicity and increase TNF's effectiveness in selectively eliminating tumor cells. TNF-α is also implicated in physiological sleep regulation. TNF-related proteins such as receptor activator for nuclear factor κB ligand (RANKL) are required for osteoclast differentiation necessary for bone resorption [16].
