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Model Based Insights into Sepsis - Dr. Jamil Ahmad
Sepsis is one of the major human diseases and can result in significant number of patient deaths every year. During infection, human immune responses tries to regulate bacterial levels in blood catered with the level of inflammation. However, in sepsis immune system could not maintain a balance between levels of bacteria and inflammation lead the patient towards multiple organ damage with eventual death. In previous studies, different opinions have been made about the role of inflammatory responses in sepsis that attracted our attention towards qualitative properties of immune signalling pathways. In some studies, inflammation is considered for the death of the patients whereas in other studies immune deficiency is associated with patient mortality.
A study “Rehan Zafar Paracha, Jamil Ahmad, Amjad Ali, Riaz Hussain, Umar Niazi, Samar Hayat Khan Tareen, Babar Aslam (2014) Formal Modelling of Toll like Receptor 4 and JAK/STAT Signalling Pathways: Insight into the Roles of SOCS-1, Interferon-β and Proinflammatory Cytokines in Sepsis” recently published in PLoS ONE by the collaborative effort of the groups supervised by Assist. Prof. Dr. Jamil Ahmad, RCMS, NUST and Assist. Prof. Dr. Amjad Ali, ASAB, NUST. This study employed the formal modelling and model-checking based verification (a framework in Systems Biology) of human signalling dynamics both in the case of sepsis and non-septic dynamics of immune signalling. Comparisons among dynamics were further supported by intervening the specific interactions among entities of immune signalling pathway.
Among the reported predictions, recurrent induction of proinflammatory cytokines with subsequent downregulation has been implicated as the basic characteristic of sepsis, which is supported by the previous studies. Moreover, it has been shown that the inflammation is followed by immunomodulation in septic patients and the downregulation of proinflammatory cytokines by SOCS-1 is desirable to boost the immunity. On the other hand, interventions either in some of the signalling events such as in TLR4 or transcriptional elements such as NFκB and STAT have been implicated as effective in the downregulation of immune responses. Whereas, IFN-β and SOCS-1 mediated downregulation at different levels of signalling were associated with the variations in the levels of proinflammatory cytokines at different periods of disease stage.