Interleukin-10 levels are often elevated in serum of adults with Hodgkin'sdisease and are associated with inferior failure-free survival

Background: Interleukin-10 (IL-10) is a pleiotropic cytokine that protects B- or T-lymphocytes and hemopoietic progenitors from apoptosis induced by d oxorubicin, glucocorticoids, or deprivation of growth factors. IL-10 is als o immunosupressive, and tumor cells secreting IL-10 can grow in syngeneic o r allogeneic hosts, and can inhibit the generation of tumor-specific cytoto xic T cells. Hodgkin-Reed-Sternberg cells are derived from follicular cente r B cells and they may be latently infected by EBV. When this occurs they o ften express IL-10. Based on these considerations we investigated the relat ionship between pretreatment serum IL-10 levels and failure-free survival ( FFS) in Hodgkin's disease (HD). Patients and methods: Untreated patients, older than 16 years, with biopsy- proven HD, were included if treated with ABVD or equivalent regimens, and i f pretreatment serum was available. IL-10 levels were determined with a cap ture enzyme-linked immunoassay specific for cellular IL-10. Results: Among healthy adult volunteers serum IL-10 levels ranged from 4.8- 9.8 pg/ml (mean 7.1, standard deviation 1.5 pg/ml). Therefore levels greate r than or equal to 10 pg/ml were considered elevated. We identified 101 pat ients with available serum. Their median age was 32 years, and 60% had B-sy mptoms. Ann Arbor stage was I in 4, II in 21, III in 35, and IV in 41 patie nts. Histology was nodular sclerosis in 74, mixed cellularity in 12, lympho cyte predominance in six, lymphocyte depletion in one, and unclassified in eight patients. Pretreatment serum IL-10 levels were elevated in 51 patient s, and were higher in those with serum albumin < 3.5 g/dl, B symptoms, seru m beta(2)-microglobulin greater than or equal to 2.5 mg/l, anemia, and AAS III or IV. After a median follow-up of 32 months for survivors, 20 patients have progressed, and the three-year FFS of those with high vs. normal seru m IL-10 was 60% +/- 9 vs. 91 +/- 9% (50% vs. 50% of the population; P = 0.0 04 by log-rank). Among patients with Ann Arbor stage III or IV the three-ye ar FFS for those with high vs. normal serum IL-10 (58 vs. 42% of the popula tion) was 57 +/- 9% vs. 92 +/- 6% (P = 0.008 by log-rank). Multivariate ana lysis using Cox's proportional hazards model confirmed that IL-10 was an in dependent variable associated with inferior FFS in this population. Conclusions: Elevation of serum IL-10 levels is frequent and is associated with inferior FFS in adults with ABVD-treated HD. This observation should b e verified in other patient populations. In addition, the source and the ro le of IL-10 in the biology of HD should be further investigated.