Quantitative immunohistochemical analysis of cytokine profiles in Epstein-Barr virus-positive and -negative cases of Hodgkin's disease.

ABSTRACT

Hodgkin's disease (HD) is a malignant lymphoproliferative disease characterized by the presence of Hodgkin-Reed-Sternberg cells surrounded by a reactive infiltrate. In Epstein-Barr virus (EBV)-associated cases (40-60%), at least two EBV-encoded proteins [latent membrane protein 1 (LMP1) and LMP2] are expressed, which are potential targets for cytotoxic T-lymphocytes (CTLs). Although in EBV-positive cases significantly more activated (granzyme B-positive) CTLs and natural killer (NK) cells are present, the cytotoxic immune response is not sufficient for adequate killing of tumour cells. The production of immunomodulating cytokines within the tumour may be one of the mechanisms causing circumvention of the immune system. This study investigated by immunohistochemistry the presence of the immunosuppressive cytokine interleukin-10 (IL-10) and other Th1/Th2-associated cytokines [IL-2, IL-4, interferon-gamma (IFN-gamma)] in the neoplastic cells and reactive lymphocytes of nine EBV-positive and 18 EBV-negative cases of HD. The percentage of IL-10-expressing cells, both neoplastic and reactive, in EBV-positive cases was significantly higher (33.1% vs. 18.5% for the neoplastic cells and 21.6% and 12.2% for the reactive cells, p=0.003 and 0.04, respectively) than in EBV-negative cases. No difference in the percentage of IL-2-, IL-4- and IFN-gamma-expressing cells was observed. These results suggest that escape from local immune surveillance is not due to a shift from Th1 towards Th2, but may be caused by a direct effect of IL-10 on the cytotoxic cells.