IL-6 and IL-10 in post-transplant lymphoproliferative disorders development and maintenance: a longitudinal study of cytokine plasma levels and T-cell subsets in 38 patients undergoing treatment

Abstract

IL-6 and IL-10 have previously been implicated in the pathogenesis of post-transplant lymphoproliferative disorders (PTLD) and, like peripheral lymphocyte populations, are markers of immune status that are amenable to study in vivo. Thus, we analyzed cytokine plasma levels as well as lymphocyte subsets in a longitudinal analysis of 38 adult transplant recipients undergoing treatment for PTLD. Pretherapeutically, we found significantly elevated IL-6 (13.8 pg/ml) and IL-10 plasma levels (54.7 pg/ml) - in the case of IL-10, even higher in treatment nonresponders than in responders (116 vs. 14 pg/ml). Over time, however, IL-10 levels did not correlate with the course of disease, whereas those of IL-6 did, falling in responders and rising in nonresponders. These findings were independent of histological EBV-status, treatment type, and total peripheral T-cell counts, which were significantly reduced in patients with PTLD. Our observations support the idea that although IL-10 is important for creating a permissive environment for post-transplant lymphoma development, IL-6 is associated with PTLD proliferation. The analysis of lymphocyte subsets further identified HLA-DR+ CD8+ lymphocyte numbers as significantly different in non-PTLD controls (33%), treatment responders (44%) and nonresponders (70%). Although the specificity of these cells is unclear, their increase might correlate with the impaired tumor-specific cytotoxic-T-lymphocyte (CTL)-response in PTLD.