Inflammation is a natural and necessary response that helps protect the body from harm, but when it goes unchecked, it can become a source of chronic pain and disease. One of the key players in this process is a protein called Tumour Necrosis Factor (TNF). While TNF helps kickstart the body’s defence mechanisms, it can also be a culprit behind ongoing inflammation linked to conditions like arthritis and autoimmune diseases. We spoke to our expert Dr Balakrishna GK, Senior Consultant - Internal Medicine, Gleneagles BGS Hospital, Kengeri, Bengaluru, who explained how TNF functions and its impact on the body.
Understanding Tumour Necrosis Factor
TNF is a pro-inflammatory cytokine produced mainly by macrophages, although it can also be secreted by other cells, such as lymphocytes and fibroblasts. “It was initially discovered for its ability to induce tumour cell death, hence the name "tumour necrosis factor." However, its functions extend far beyond tumour suppression. TNF is involved in regulating immune responses, inflammation, and cellular apoptosis,” said Dr Balakrishna.
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The Role of TNF in Inflammation
"In the context of inflammation, TNF acts as a key mediator. When the body encounters an injury or infection, TNF is released as part of the acute inflammatory response," added Dr Balakrishna. It promotes the recruitment of immune cells to the site of inflammation, enhances vascular permeability, and stimulates the production of other pro-inflammatory cytokines. This cascade of events is crucial for initiating the healing process.
According to a 2022 study, TNF not only triggers inflammatory responses by activating inflammatory gene expression but also does so indirectly by promoting cell death, leading to inflammatory immune reactions and disease progression. As a result, inhibitors of cell death are being explored as a potential new treatment for TNF-dependent inflammatory diseases.
However, while TNF is vital for combating infections and facilitating tissue repair, its dysregulation can lead to chronic inflammatory conditions. Elevated levels of TNF are associated with several autoimmune diseases, including Rheumatoid Arthritis (RA), lupus, and inflammatory bowel disease. In these conditions, the persistent presence of TNF contributes to the ongoing cycle of inflammation, causing tissue damage and chronic symptoms.
TNF in Rheumatology
TNF plays a crucial role in rheumatology. In RA, the joint tissues are infiltrated by inflammatory cells, and TNF levels become markedly elevated. This leads to synovitis, cartilage destruction, and ultimately joint deformities. The understanding of TNF's role in these processes has revolutionised treatment approaches.
Biologic therapies targeting TNF, known as TNF inhibitors, have become cornerstone treatments for managing RA and other inflammatory diseases. "These medications, such as infliximab, etanercept, and adalimumab, effectively block the action of TNF, leading to reduced inflammation and improved patient outcomes. Clinical studies have shown that TNF inhibitors not only relieve symptoms but also halt the progression of joint damage, offering significant benefits to patients," explained Dr Balakrishna.
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Caution and Advisory on TNF Inhibitors
Although TNF inhibitors are highly effective in treating inflammatory conditions, they are not suitable for everyone. Special caution is required for people in an immunosuppressive state or with certain infections. “Conditions like Tuberculosis (TB) present significant risks when using these medications, as TNF inhibition can reactivate latent infections. In such cases, these medications are either not advised or used with careful monitoring and under strict medical supervision,” warned Dr Balakrishna.
Furthermore, patients with HIV infection, those taking steroid medications, or individuals with severe sepsis, certain cancers, or diabetes are considered high-risk for TNF inhibitor therapy. The decision to use TNF inhibitors in these populations requires a calculated risk assessment, with the benefits weighed carefully against potential complications.
The Link Between TNF and Other Inflammatory Conditions
Beyond rheumatology, TNF is implicated in various inflammatory conditions, including psoriasis, ankylosing spondylitis, and even conditions like Crohn's disease and ulcerative colitis. In each of these diseases, the dysregulation of TNF contributes to chronic inflammation and associated symptoms.
“Moreover, recent research has also suggested a role for TNF in metabolic disorders. For example, chronic inflammation mediated by TNF is linked to insulin resistance and obesity, highlighting the cytokine's involvement in broader health issues,” added Dr Balakrishna.
Bottomline
Dr Balakrishna concluded, “The link between tumour necrosis factor and inflammation is complex yet crucial for understanding various health conditions, especially in rheumatology. While TNF is essential for initiating and regulating inflammatory responses, its overproduction can lead to chronic inflammation and tissue damage.”
“As a physician treating rheumatology cases, I have firsthand experience with the significant impact of TNF on patient health and the remarkable benefits of targeted therapies. However, caution is essential when treating immunosuppressed patients or those with infections like TB, as TNF inhibitors require close monitoring. Continued research is shedding light on the many roles TNF plays in inflammation and its promise as a therapeutic target,” he added.
[Disclaimer: This article contains information provided by an expert and is for informational purposes only. Hence, we advise you to consult your own professional if you are dealing with any health issues to avoid complications.]