Tnf, also known as Tumour Necrosis Factor α, is a classical pro-inflammatory cytokine. It is involved in various physiological and pathological processes, such as immunity, inflammation, and apoptosis. TNF-α exerts its biological activities through binding to Types 1 and 2 TNF receptors (TNF-R1 and -R2), and the signaling pathway is associated with many diseases [1,3].

In myocarditis, mice with genetic deletion of Tnf (Tnf+/- and Tnf-/-) showed reduced myocarditis incidence, but susceptible animals developed extensive heart inflammation. In the transgenic T cell receptor (TCRM) model, defective Tnf production was associated with increased mortality at a young age due to cardiomyopathy and cardiac fibrosis. This indicates that Tnf promotes myocarditis development by activating cardiac endothelial cells, yet protects from exacerbating cardiac inflammation by inducing activation-induced cell death of heart-reactive effector CD4+ T cells in established disease [2].

In conclusion, Tnf is a crucial cytokine in the body, playing a complex role in inflammation and disease. The use of Tnf knockout mouse models in myocarditis research has revealed its dual-edged sword function in promoting and protecting against disease progression, providing insights into the underlying mechanisms and potential therapeutic strategies for heart-related diseases.