The influence of interleukin-10 and interleukin-18 on interferon-gamma production by peritoneal exudate cells in patients with gastric carcinoma

Although the peritoneal cavity (PC) is the most common site of metastasis in gastric carcinoma, its immune status in patients with advanced cancer remains largely unknown. We investigated the relationship between clinical parameters and cytokine levels in the PC and also evaluated IFN-y production by peritoneal exudate cells (PEC), obtained during surgery from patients with stage III-IV gastric carcinoma. Although the IFN-gamma and IL-12 levels in the PC did not differ between stage III and stage IV cancer patients, the latter had higher levels of IL-10 and IL-18. Those patients with higher IFN-gamma levels experienced a significantly better survival-rate than those with lower IFN-gamma levels, whereas IL-18 (but not IL-10) levels were inversely-correlated with survivaL IFN-gamma levels increased in parallel with IL-18 levels in patients who survived more than two years, but this correlation did not apply to patients who died of disease within two years. In addition, anti-CD3-Ab or cytokine- stimulated PEC from patients with low IL-10 levels in their PC produced a significantly greater amount of IFN-gamma than PEC from patients with high PC IL-10 levels. In conclusion, a high level of IFN-y in the PC is an indicator of favorable outcome. Both IL-10 and IL-18 levels in the PC increased with tumor progression. Although the number of PEC capable of producing IFN-gamma increases with tumor progression, their ability to secrete IFN-gamma in response to IL-18 may be influenced by local IL-10 levels in the PC.