Interleukin-22, liver progenitor cells, and liver cancer


  • Potential conflict of interest: Nothing to report.

  • This work was supported by the intramural program of the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health (AA000369-07).

To the Editor:

We read the discussion about interleukin (IL)-22 as a negative prognostic indicator in viral hepatitis-related hepatocellular carcinoma (HCC).[1] It is clear that IL-22 is a hepatoprotective cytokine. A phase I clinical trial of IL-22 has been carried out ( On the other hand, Radaeva et al. reported that IL-22 also promoted human HCC growth by activating signal transducer and activator of transcription 3 (STAT3) and subsequently up-regulating STAT3 target genes,[2] which was confirmed by others.[3] Recently, our group reported that IL-22 transgenic (Tg) mice developed more and larger liver tumor after diethylnitrosamine injection.[4] Interestingly, IL-22 Tg mice did not spontaneously develop liver tumors. These findings suggest that IL-22 alone does not initiate liver tumors, but can promote hepatic carcinogenesis together with other risk factors.

We recently demonstrated that IL-22 can also promote the growth of liver progenitor cells (LPCs), which partially explains the expansion of LPCs in chronic viral hepatitis patients resulting from higher IL-22 levels in these patients.[5] LPCs are considered as an important source of liver cancer stem cells. To test whether IL-22-induced LPC expansion contributes to carcinogenesis, we fed wild type (WT) and IL-22 Tg mice with a 3,5-diethoxycarbonyl-1,4-dihydro-collidin diet for 7 months. Only 1 of 4 IL-22 Tg mice developed liver tumor, compared to 0 of 4 in WT mice. Although our study is preliminary, it suggests that additional factors are necessary for the transformation from LPCs to liver cancer stem cells (LCSCs). The hypothesis was supported by a study that found that increased tumorigenicity was discovered in LPCs with hepatitis B virus x protein expression.[6]

Taken together, elevated IL-22 can promote the growth of LPCs and HCC. However, in addition to IL-22, other factors, such as viral infection, are necessary for the transformation of LPCs to LCSCs and subsequent HCC initialization.

  • Dechun Feng, Ph.D.

  • Laboratory of Liver Diseases

  • National Institute on Alcohol Abuse and Alcoholism

  • National Institutes of Health

  • Bethesda, MD