Cytokine-induced inflammatory liver injuries

Area of Science:

• Immunology
• Hepatology
• Cytokine Biology

Background:

• Interleukin-18 (IL-18) is a cytokine produced by macrophages, including Kupffer cells, and influences immune responses.
• IL-18 can induce both pro-inflammatory (IFN-gamma) and allergic (IL-4) pathways, activating immune cells like T helper cells, mast cells, and basophils.
• Elevated IL-18 levels are linked to inflammatory conditions such as Crohn's disease, atherosclerosis, atopic dermatitis, and critically, various liver diseases.

Purpose of the Study:

• To review the role of Interleukin-18 (IL-18) in the pathogenesis of liver injuries.
• To examine the involvement of Natural Killer T (NKT) cells in IL-18-mediated liver damage.
• To consolidate current understanding of IL-18 and NKT cell contributions to liver pathology.

Main Methods:

• Review of existing literature on IL-18 and NKT cell functions in liver injury models.
• Analysis of studies investigating endogenous IL-18 in experimental liver diseases (e.g., endotoxin-induced injury, Fas ligand-induced hepatitis).
• Examination of clinical data correlating serum IL-18 levels with liver disease severity in patients.

Main Results:

• Endogenous IL-18 is crucial for inducing experimental liver injuries in mice.
• Serum IL-18 levels positively correlate with disease severity in human liver conditions like fulminant hepatitis and cirrhosis.
• NKT cells, abundant in the liver, are implicated in specific types of hepatitis.

Conclusions:

• Endogenous IL-18 plays a significant role in the development of diverse liver injuries in both murine models and humans.
• NKT cells are key mediators in certain liver injuries, interacting with pathways involving IL-18.
• Further research into IL-18 and NKT cell interactions is vital for understanding and potentially treating liver diseases.