Tnf, also known as Tumour necrosis factor α, is a classical pro-inflammatory cytokine. It is involved in numerous physiological and pathological processes, playing a significant role in immunity, inflammation, and apoptosis [1,2,3,4]. TNF binds to two specific receptors, TNF-receptor type I (TNF-R1) and TNF-receptor type II (TNF-R2), triggering complex signaling pathways that can lead to both cell death and survival signals [4].

In the context of myocarditis, mice with genetic deletion of Tnf (Tnf+/- and Tnf-/-) were used as KO mouse models. Tnf+/- and Tnf-/- mice immunized with α-myosin heavy chain peptide showed reduced myocarditis incidence, but the susceptible animals developed extensive heart inflammation. In the TCRM model, defective Tnf production was associated with increased mortality at a young age due to cardiomyopathy and cardiac fibrosis. This indicates that Tnf signaling promotes myocarditis development by activating cardiac endothelial cells, yet in established disease, it protects from exacerbating cardiac inflammation by inducing activation-induced cell death of heart-reactive effector CD4+ T cells [1].

In conclusion, Tnf is a crucial cytokine in regulating immune and inflammatory responses. The study of Tnf KO mouse models has revealed its dual-edged role in myocarditis, highlighting its complex function in disease development and progression. This understanding contributes to explaining the lack of success of standard anti-Tnf therapy in heart failure patients and may open perspectives for T cell-targeted approaches [1].