Elevated Serum Levels of IL-10 are Associated with Inferior Progression-Free Survival in Patients with Hodgkin's Disease Treated with Radiotherapy

Abstract

Elevated pretreatment serum interleukin-10 (IL-10) is associated with inferior progression-free survival (PFS) in patients with Hodgkin's disease (HD) treated with ABVD or equivalent regimens. Therefore, we explored the association of serum IL-10 with presenting features and PFS in HD patients treated only by radiotherapy (RT) with curative intent. Eligible patients were previously untreated, had biopsy-proven HD, were older than 16 years, HIV-negative, and had unthawed pretreatment serum. Serum IL-10 levels were measured with ELISA and were considered high if > or = 10 pg/ml. We identified 69 patients with median age of 34 years (range 16 - 74), of who 52% were males, and 3% had B-symptoms. Ann Arbor Stage was I in 35%, II in 58%, and III in 7% of the patients. Histology was lymphocyte predominance in 26%, and classical HD in 74% of the patients. Serum IL-10 was elevated in 35% of the patients. After a median follow-up of 67 months for survivors, the 5-year PFS of patients with high vs. normal serum IL-10 was 50% vs. 81% (all patients, P = 0.006), and 43% vs. 77% for the subset with classical HD (P = 0.008). Multivariate analysis revealed that high serum IL-10 and beta2-microglobulin were independently associated with inferior PFS. Patients with none, 1, or 2 adverse features comprised 57%, 36%, and 7% of the population, and their 5-year PFS was 80%, 63%, and 0%, respectively (P < 0.0001). In conclusion, high serum IL-10 is independently associated with inferior PFS in patients with HD treated with RT.

Impact of interleukin-10 polymorphisms ( 1082 and 3575) on the survival of patients with lymphoid neoplasms

“…2,3,5,6 This is in agreement with our observations and can help to explain why patients with the IL10-3575AA genotype have a better overall survival. However, we did not have measurements of IL-10 production and a more detailed statistical analysis was limited by the small number of cases in each lymphoma category.…”

“…It has also been described that patients with high IL-10 production have a worse prognosis. 3,5,6 A number of polymorphisms of the IL-10 gene promoter have been described. These include two biallelic polymorphisms at positions -1082 (G to A substitution), and -3575 (T to A substitution).…”

High serum levels of B‐lymphocyte stimulator are associated with clinical–pathological features and outcome in classical Hodgkin lymphoma

“…In our opinion, the lack of a significant association between serum levels of BLyS and IL-10, which has been reported as a marker that is strictly related to disease activity (Visco et al, 2004), may be due either to the small number of our series or to an independent role of these two molecules in HL.…”

“…Interestingly the same group, Chiu et al (2007) has demonstrated that the signals (Novak et al, 2002(Novak et al, , 2004a. Furthermore, an involvement of BLyS in HL was suggested by the fact that IL-10, a pleiotropic cytokine also involved in HL pathogenesis (Visco et al, 2004), regulates BLyS expression and release by myeloid cells (Nardelli et al, 2001). Among NHL patients, a significant correlation between high pre-treatment sBLyS levels and the presence of B symptoms, elevated LDH and an inferior overall survival has been previously demonstrated only in diffuse large B-cell lymphoma (DLBCL) (Novak et al, 2004b).…”

Quantificação das citocinas séricas Th1/Th2 por citometria de fluxo no linfoma de Hodgkin clássico

“…Esses autores sugerem que a IL-10 sérica poderia ser considerada um fator prognóstico independente das variáveis clínico-laboratoriais clássicas, consideradas pelo IPI, e que a esta citocina poderia auxiliar na identificação precoce de pacientes que necessitariam de tratamento mais agressivo ao diagnóstico. 5,[9][10][11][12][13][14][15][16][17] Sabe-se que a IL-10 é produzida por linfócitos Th2 e tem função inibitória sobre a produção de INF-γ e IL-2, regulando negativamente a imunidade celular Th1. 6,8 Portanto, de acordo com os nossos resultados e os dados da literatura, a IL-10 sérica elevada, no grupo de pacientes com variáveis que implicam pior prognóstico, poderia estar regulando ne-gativamente uma resposta imune Th1 ou citotóxica, contribuindo assim com a progressão da doença.…”