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Endotoxin stimulates hepatocyte interleukin-6 production
N Panesar1, K Tolman, J E Mazuski
1Department of Surgery, DVA Medical Center, St. Louis, Missouri, USA.
The Journal of Surgical Research
|July 29, 1999
Summary
Murine hepatocytes release significant amounts of interleukin-6 (IL-6) when exposed to endotoxin or proinflammatory cytokines. This suggests hepatocytes are a key source of IL-6 during inflammatory responses.
Area of Science:
- Immunology
- Cell Biology
- Hepatology
Background:
- Interleukin-6 (IL-6) is a key cytokine in the acute phase response.
- While macrophages are known producers, epithelial cells also release IL-6.
- The role of hepatocytes in IL-6 production requires further investigation.
Purpose of the Study:
- To determine if hepatocytes release IL-6 when stimulated by endotoxin and proinflammatory cytokines.
- To investigate the cellular source of IL-6 in cultured hepatocytes.
Main Methods:
- Cultured murine hepatocytes were treated with lipopolysaccharide (LPS), interleukin-1 (IL-1), or tumor necrosis factor (TNF).
- Inhibitors including IL-1 receptor antagonist (IL-1 RA), anti-TNF antibody, and dexamethasone were used.
- IL-6 levels in culture supernatants were measured by ELISA, and cellular sources were identified via immunohistochemistry.
Main Results:
- LPS, IL-1, and TNF significantly increased IL-6 production by hepatocytes.
- Combinations of LPS with IL-1 or TNF showed synergistic effects on IL-6 release.
- Dexamethasone inhibited LPS-induced IL-6 production, while IL-1 RA and anti-TNF antibody did not.
- Immunohistochemistry confirmed hepatocytes as the primary source of IL-6.
Conclusions:
- Murine hepatocytes are a significant source of IL-6 when stimulated by endotoxin and proinflammatory cytokines.
- LPS directly stimulates hepatocyte IL-6 production, independent of IL-1 or TNF mediation.
- Hepatocytes play a direct role in the inflammatory response through IL-6 production.