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Cytokine-induced inflammatory liver injuries.

H Tsutsui¹, K Adachi, E Seki

¹Hyogo College of Medicine, Nishinomiya 663-8501, Japan.

Current Molecular Medicine

|October 7, 2003

Summary

Interleukin-18 (IL-18) drives both inflammatory and allergic responses, significantly contributing to various liver injuries in mice and humans. This review explores IL-18

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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.

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