scovered that normal female mice given DEN produced far less IL-6 than the males. Comparing the normal mice to knockout mice missing the IL-6 cytokine, the scientists found that when knockout mice were given DEN, both males and females developed liver cancer at the same, lower, rates.
By eliminating IL-6, we reduced the incidence of liver cancer in the males by close to 90%, Karin said. However, the missing IL-6 made no further difference in female mice.
The researchers then treated normal male mice with estrogen, and exposed them to DEN. The IL-6 level in those males was reduced to the same level as in female mice, as was the degree of liver injury. Experiments on specialized cells in the liver that produce IL-6 showed that estrogen acts on these cells to suppress IL-6 production.
A similar mechanism may account for the gender bias in liver cancer in humans, according to the researchers. Their discovery could lead to development of therapies to reduce development of liver cancer in males by either decreasing the levels IL-6 in males, interfering with IL-6 action or by administering estrogen-like compounds to males in order to inhibit production of IL-6.
"While some organs, such as breasts, are clearly influenced by gender, others like the liver are not, said Naugler. So its quite interesting that liver inflammation is so markedly suppressed by estrogens.
It raises the possibility that organs not usually associated with gender differences may be governed by the same principle. Bladder cancer, for example, occurs more frequently in males than females, and the differences may be a result of higher IL-6 levels and inflammation in male bladders."
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