Therapeutic use of specific tumour necrosis factor inhibitors in inflammatory diseases including COVID-19

Abstract

Coronavirus disease 2019 (COVID-19) has caused significant devastation globally. Despite the development of several vaccines, with uncertainty around global uptake and vaccine efficacy, the need for effective therapeutic agents remains. Increased levels of cytokines including tumour necrosis factor are significant in the pathogenesis of COVID-19 and associated with poor outcomes including ventilator requirement and mortality. Repurposing tumour necrosis factor blocker therapy used in conditions such as rheumatoid arthritis and inflammatory bowel disease seems promising, with early feasibility data showing a reduction in circulation of pro-inflammatory cytokines and encouraging the evaluation of such interventions in preventing disease progression and clinical deterioration in patients with COVID-19. Here, we examine the biological activities of tumour necrosis factor inhibitors indicative of their potential in COVID-19 and briefly outline the randomised control trials assessing their benefit-risk profile in COVID-19 therapy.

COVID-19 infection: an overview on cytokine storm and related interventions

“…In other words, all five antagonists obstruct interaction between TNF and corresponding receptors on expressed cells. More details about these antagonists are depicted in Table 1 [ 126 ]. In addition, it has been reported that IL-17A and TNF-α have a substantial role in lung damage of covid-19 disease with obesity [ 127 ].…”

Anti-Inflammatory Azaphilones from the Edible Alga-Derived Fungus Penicillium sclerotiorum

“…TNF-α is considered a critical cytokine in COVID-19–associated cytokine storm of acute inflammation, inflammatory bowel disease of chronic inflammation, and rheumatoid arthritis in autoimmune disease [ 18 ]. In order to test compounds with a potential effect on preventing inflammation from deteriorating, the TNF-α-induced NFκB phosphorylation was tested by immunoblotting ( Figure 5 A).…”

Molecular signaling pathways, pathophysiological features in various organs, and treatment strategies in SARS-CoV2 infection

“…Several studies have shown that TNF-α is the most important factor in the pathogenesis of COVID-19 infection. TNF-α, an important pro-inflammatory cytokine, can regulate various cellular biological processes, such as differentiation, proliferation, and immune response ( Patel and Wadhwa, 2021 ). Several mechanisms have been proposed to describe the molecular mechanism of TNF-α in COVID-19 infection.…”

“…Another mechanism is the activating the cells of the innate immune system and macrophages as the main producers of TNF-α, which is predominantly elevated in the serum of COVID-19 infected patients. TNF-α, produced by macrophages in viral infections, can regulate innate immune system activity, stimulate other macrophages, natural killer cells, dendritic cells, and neutrophils, and inhibit viral replication ( Patel and Wadhwa, 2021 ). TNF-α can cause leukocyte chemotaxis by activating endothelial cells and inducing them to secrete chemokines.…”