Investigation of ameliorative role of IL-6 and IL-22 of in Hepatitis B associated Hepatocellular carcinoma

Abstract

Hepatocellular carcinoma, a neoplasm characterized by the unregulated proliferation of hepatocytes, has emerged as a prominent etiology of cancer-associated mortality on a global scale. A considerable part of hepatocellular carcinoma (HCC) cases is closely linked to infection caused by the Hepatitis B Virus (HBV), emphasizing the investigation of the processes that connect chronic HBV infection with the progression of of Hepatocellular carcinoma. Many factors might contribute to the development of an unresolved state of inflammation, which ultimately elevate the possibilities of hepatocellular carcinoma (HCC) including pro-inflammatory cytokines found in the tissues promoting its development and progression. The majority of these cytokines are involved in the process of cancer cell production by promoting cellular proliferation, facilitating angiogenesis. Interleukin 6 (IL-6) and Interleukin-22 serve an important role in orchestrating immune responses to combat infections. It has dual functionality as both a pro-inflammatory and anti-inflammatory cytokine. IL-6 has been recognized as a promoter of cancerous cell proliferation. The impaired hepatic function impedes the elimination of interleukin-6 (IL-6), leading to heightened concentrations of this cytokine in the circulatory system. Elevated concentrations of interleukin-6 (IL-6) possess the capacity to induce amplification of cytotoxic T-cells, initiate hepatic inflammation, and result in immune cell death. In vitro studies confirmed the tumor-promoting and antiapoptotic actions of interleukin-22 (IL-22) and interleukin-6 (IL-6). This research study was targeted to in-silico studies in order to verify the in-depth performance of mentioned interleukins in the aspect of infection caused by hepatitis B virus. We designed the Model for locating the target sites of action for IL-6 and IL-22 to represent their role in the maintenanace of liver metabolism and the prevention of the liver infection progression towards Liver Carcinoma. We underwent the in-depth literature survey to extract the detailed pathways for Hepatitis b infection and hepatocellular carcinoma as well as role of IL-6 and IL-22 in these pathways. Later on we performed pathway modeling by simbiology MTLAB which paved the way for pathway analysis by studying the dosage responses as well as calibrated simulations representing the time dependent and dosage dependent roles of IL-6 in upregulating and downregulating various genes involves in the HBV pathway. Analyis showed the Role of IL-6 in preventing the viral entry and viral transcription in liver cells as well represented the role anti-apoptotic and anti-cancerous role of IL-22 via P13K/AKT pathway while IL-22 was identified as interleukin playing role in liver regeneration by enhancing the expression of genes playing role in the differentiation of cells as well as their proliferation.