Differential cytokine expression in EBV positive peripheral T cell lymphomas

Aim-To investigate whether specific cytokines are secreted locally at the t umour site in Epstein-Barr virus (EBV) positive peripheral T cell lymphoma (PTCL). Methods-An RNase protection assay system was used to study the differential expression of 21 cytokines in parallel in eight cases of EBV positive non- nasal PTCL, and compared with 11 EBV negative non-nasal PTCLs and three EBV positive nasal natural killer (NK) cell lymphomas. Results-Among the eight EBV positive cases, interferon gamma (IFN-gamma), l ymphotoxin beta (LT beta), interleukin 10 (IL-10), tumour necrosis factor a lpha (TNF-alpha), transforming growth factor (TGF-beta 1), and IL-1 recepto r alpha (IL-Ra) were frequently detectable. IL-15, IL-6, IL-4 , IL-1 beta, TNF-beta, and IL-9 were sporadically detectable. Of the frequently detectab le cytokines, IFN-gamma and LT beta were commonly detected in the EBV negat ive cases. For cases with > 50% EBV encoded small non-polyadenylated RNA (E BER) positive cells, IL-10, TNF-alpha, and TGF-beta 1 were detected in thre e of three cases, and IL-1Ra in two of three cases. For cases with < 20% EB ER positive cells, IL-10 was detected in three of five cases, TNF-alpha in two of four cases, but TGF-beta 1 and IL-1Ra were not detected. Interesting ly, IL-6 was detected in two of three cases with > 50% EBER positive cells, but only in one of five cases with < 20% EBER positive cells. For comparis on, in NK cell lymphomas, IL-10, TNF-alpha, IL-1Ra, and IL-6 were all detec table, but TGF-beta 1 was not detected at all. Immunohistochemical staining revealed IL-10 in many cells; in contrast, EBV latent membrane protein 1 ( LMP1) was only found to be positive in isolated cells. Conclusions-Certain cytokines, such as IL-10 and TNF-alpha, might be expres sed preferentially in EBV positive peripheral T cell lymphomas. It is likel y that such a cytokine environment enhances EBV infection and contributes t owards tumorigenesis.