1. TNF-Alpha in Cancer Treatment
TNF-α can kill or slow the growth of some tumour cells, though its effects vary across different cell types. For example, combining TNF-α with chemotherapy agents like dactinomycin can increase its tumor-killing effects. However, tumours in living organisms may resist TNF-α, sometimes due to high levels of endogenous TNF-α or other resistance mechanisms. Macrophages, with TNF-α on their surface, also contribute to targeting cancer cells.
2. TNF-Alpha and Infection Control
TNF-α is also a crucial component of the immune system’s response to infections, particularly viral infections. It helps destroy virus-infected cells by boosting neutrophil activity and inhibits the replication of viruses such as influenza. Furthermore, TNF-α plays a role in generating fever as a part of the body’s defence mechanism against infections.
3. Regulation of Immune System
TNF-α is central to regulating the immune system. It’s involved in various autoimmune diseases, including lupus and Sjögren’s syndrome, where its levels are often elevated. By influencing immune cells, TNF-α can drive both immune activation and immune suppression, which is critical for understanding its role in cancer and autoimmune diseases.
The Role of TNF-Alpha in Inflammation
1. Septic Shock and Systemic Inflammation
Excessive TNF-α production due to bacterial infections can lead to septic shock, causing widespread inflammation, organ failure, and high mortality. It also contributes to liver damage during viral infections, like hepatitis.
2. Cachexia and Metabolic Disorders
TNF-α, sometimes called cachectin, is associated with cachexia, a syndrome of weight loss and muscle wasting commonly seen in cancer patients. It contributes to metabolic changes that result in severe weight loss and muscle breakdown, exacerbating the physical decline of cancer patients, especially in advanced stages.
3. TNF-Alpha and Virus Replication
TNF-α has antiviral properties similar to other immune molecules like interferon (IFN). It can prevent the replication of various viruses by inhibiting early viral protein synthesis. TNF-α also collaborates with other cytokines like TNF-β (or TNF-gamma) to combat viral infections. For example, in HIV-infected T cells, TNF-α can activate the NF-κB pathway, which is crucial for HIV gene expression and viral replication. The increased TNF-α levels in patients with AIDS demonstrate its involvement in the immune response to viral infections. Additionally, TNF-α exhibits antibacterial and antimalarial effects.
