Role of inflammasomes and cytokines in immune dysfunction of liver cirrhosis.

Liver cirrhosis develops as a result of persistent inflammation and liver injury. The prolonged inflammation triggers the buildup of fibrous tissue and regenerative nodules within the liver, leading to the distortion of the hepatic vascular structure and impaired liver function. Cirrhosis disrupts the ability of liver function to maintain homeostasis and hepatic immunosurveillance which causes immunological dysfunction in the body. In pathological conditions, the production of cytokines in the liver is carefully regulated by various cells in response to tissue stimulation. Cytokines and inflammasomes are the key regulators and systematically contribute to the development of cirrhosis which involves an inflammatory response. However, the crosstalk role of different cytokines in the cirrhosis progression is poorly understood. Tumour necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), and interferon-gamma (IFN-γ), among others, are proinflammatory cytokines that contribute to liver cell necrosis, which in turn causes the development of fibrosis. While IL-10 exhibits a potent anti-inflammatory effect on the liver by inhibiting immune cell activation and neutralizing pro-inflammatory cytokine activity. Inflammasomes have also been implicated in the profibrotic processes of liver cirrhosis, as well as the production of chemokines such as CCL2/MCP-1. It is evident that inflammasomes have a role in the proinflammatory response seen in chronic liver illnesses. In conclusion, cirrhosis significantly impacts the immune system, leading to immunological dysfunction and alterations in both innate and acquired immunity. Proinflammatory cytokines like TNF-α, IL-1β, IL-6, and IFNγ are upregulated in cirrhosis, contributing to liver cell necrosis and fibrosis development. Managing cytokine-mediated inflammation and fibrosis is a key therapeutic approach to alleviate portal hypertension and its associated liver complications. This review attempted to focus largely on the role of immune dysfunction mediated by different cytokines and inflammasomes involved in the progression, regulation and development of liver cirrhosis.

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Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Subhash Medhi reports equipment, drugs, or supplies was provided by Gauhati University Faculty of Technology.