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Iron overload impairs pro-inflammatory cytokine responses by Kupffer cells

Olynyk, J.K. and Clarke, S.L. (2001) Iron overload impairs pro-inflammatory cytokine responses by Kupffer cells. Journal of Gastroenterology and Hepatology, 16 (4). pp. 438-444.

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Aim: The aim of the present study was to determine the effect of chronic iron overload on Kupffer cell cytokine production.

Methods: Kupffer cells were isolated from rats that were fed either a control or iron-supplemented diet for 12 months. Cytokine mRNA and protein levels were determined by using a ribonuclease protection assay and ELISA, respectively.

Results: Baseline levels of tumor necrosis factor-α, transforming growth factor-β1, interleukin-6 and granulocyte macrophage colony stimulating factor were similar in iron-loaded and control Kupffer cells. Following the addition of lipopolysaccharide to control cells, tumor necrosis factor-alpha, interleukin-1α and interleukin-6 mRNA levels increased. Tumor necrosis factor-alpha mRNA and protein levels were reduced by 40 and 60%, respectively, in iron-loaded cells compared with controls following the addition of lipopolysaccharide. Interleukin-6 mRNA levels in iron-loaded Kupffer cells were also reduced. Granulocyte macrophage colony stimulating factor mRNA levels remained unchanged in controls, but were significantly elevated in iron-loaded cells. Tumor growth factor-β1 mRNA and protein levels were similar in control and iron-loaded cells.

Conclusion: Deposition of iron in Kupffer cells in chronic dietary iron overload results in an impaired pro-inflammatory cytokine response to lipopolysaccharide. Our observations may have relevance to the altered immune function observed in chronic iron-overload syndromes.

Publication Type: Journal Article
Publisher: Wiley-Blackwell
Copyright: © 2001 Blackwell Science Asia Pty Ltd
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