The immune response to hepatic malignancy is likely to be determined by several factors,
including cytotoxic T-cells and the local cytokine profile. A predominantly proinflammatory-IFN-γ
(Th1) response promotes tumour rejection, while an anti-inflammatory-IL-10(Th2) response
promotes tolerance and tumour progression. It has also been suggested that T-regulatory
cells producing large amounts of IL-10, TGF-β and IL-13 suppress the inflammatory
response. We examined levels of regulatory cytokines; TGF-β, IL-10 and IL-13 and the
Th1 cytokine IFN-γ in tumour-bearing and normal liver. Normal controls obtained from
donor organs (n=11) and tumour-bearing liver (n=12) obtained at the time of resection
of colorectal metastases, were snap frozen, powdered, protein was extracted and cytokine
levels were quantified using a modified ELISA. Relatively high levels of both TGF-β
and IL-13 were detected in normal liver tissue compared to IL-10 (25.03, 54.87 and
1.73ng/100mg protein respectively). This may contribute to the tolorogenicity seen
in the liver transplant setting. The Th2/regulatory cytokine, IL-10, was significantly
raised in hepatic malignancy (12.74 vs. 2.31ng/100mg protein, p<0.0001). Despite a
large amount of IFN-γ in tumour-bearing liver, the IFN-γ:IL-10 ratio was 1.37:1, as
compared to 4.35:1 in normal liver reflecting the greater IL-10 levels in tumour samples.
TGF-β and IL-13 levels were significantly reduced in tumour-bearing compared to normalliver
(p<0.05). Our results suggest a shift towards a Th2-response in tumour-bearing liver.
IL-10 but not TGF-β/IL-13 is involved in the suppression of host antitumour responses,
facilitating tumour progression. Anti-IL-10 may be a useful therapeutic strategy in
the treatment of colorectal metastatic disease.
