A mathematical model to account for quantitative iterative effect of TNF-α positive feedback mechanism on inflammatory cascade in TLR-4 mediated TNF-α signaling pathway

Sepsis is a complex systemic biological event that is mediated by an uncontrolled cascade of inflammatory cytokines. Whilst endogenous mediators such as TNF-α, Interleukin 1 (IL1) and 6 (IL6) may play a beneficial role in controlling infection by localising the initial insult, uncontrolled increases of these cytokines are associated with deleterious events which may result in capillary leakage, coagulopathy and catastrophic organ failure. TNF-α is known to be a principal effecter molecule in the onset of serious inflammatory conditions and consequently an increased understanding of the biological pathways controlling the expression of this cytokine is essential for the development of appropriate therapeutic interventions. The purpose of this study was to use a system-theoretic approach to analyse the effect of TNF-α positive feedback mechanisms in response to the modulation of sTNF receptor 1 by quantitative and qualitative modelling of putative TLR-4 mediated TNF-α signalling pathway