Profile of cytokine expression in nasopharyngeal carcinomas: A distinct expression of interleukin 1 in tumor and CD4(+) T cells

Nasopharyngeal carcinoma (NPC) is an epithelial cancer that is causally ass ociated with Epstein-Barr virus (EBV) infection, NPC tumor biopsies are cha racterized histopathologically by an abundant infiltration of nonmalignant lymphocytes. We analyzed the expression of various cytokines in NPC tissues to investigate the interaction of the infiltrating lymphocytes and tumor c ells, Analysis using reverse transcriptase-PCR revealed the expression of a panel of cytokines in the NPC biopsies: interleukin (IL)-1 alpha, IL-1 bet a, IL-2, IL-4, IL-5, IL-6, IL-10, IFN-gamma, tumor necrosis factor-alpha, t ransforming growth factor-beta, and IL-1 receptor types I and II. Elevated expression of IL-1 alpha and IL-1 beta was observed in primary tumors and N PC metastases compared to control tissues. Interestingly, this increased ex pression correlated with the EBV-encoded viral IL-10 transcript. To determi ne which cells were responsible for producing IL-1, we determined the cellu lar constituents of NPC biopsies by immunoflow cytometric analysis. On the basis of data from these analyses, the three major specific cell population s, epithelial cells, CD4(+) T cells, and CD8(+) T cells, were selected from five NPC tumors using specific, antibody-coated paramagnetic beads. Revers e transcriptase-PCR of RNA from these fractionated cells showed that transc ripts of IL-1 alpha and IL-1 beta were present not only in the malignant ep ithelial cells but also in CD4(+) T cells infiltrating the tumor, a finding confirmed by immunohistochemical staining. We hypothesize that the unusual synthesis of IL-1 alpha and IL-1 beta by EBV-positive epithelial cells as well as by CD4(+) T cells might contribute to lymphocyte infiltration and/o r tumor growth during NPC development.