Abstract 1762: Clinical relevance of plasma IL-6 and IL-6 levels in chronic lymphocytic leukemia (CLL)

Abstract

Abstract It has been suggested that cytokines play an important role in the survival and proliferation of chronic lymphocytic leukemia (CLL) cells and these growth factors may be derived from a variety of cell types, including CLL cells. The plasma levels of the inflammatory cytokines, IL-6 and IL-8, vary in CLL and increased levels have been associated with a poor prognosis. This phenomenon has been related to the inhibition of apoptosis of CLL cells by the cytokines. In the present study, plasma IL-6 levels were measured by an ELISA assay in 193 CLL patients (107 males, 86 females; ages, 37-92 yr (median, 67.6 yr)) and the plasma IL-8 levels in 66 patients (31 males, 35 females; ages, 37-92 yr (median, 69 yr)). Samples were obtained from patients followed in the CLL Clinic at CancerCare Manitoba. Among the patients, plasma IL-6 levels ranged from < 0.01 to 1058 pg/mL, with a median value of 5.23 pg/mL. The median plasma IL-6 level in 37 age- and sex-matched controls was significantly lower at 0.83 pg/mL (range, 0.06-8.11 pg/mL)). Plasma IL-8 levels in the patients ranged from <0.01 to 1058 pg/mL, with a median value of 5.23 pg/mL. There were 22 normal age- and sex-matched controls for IL-8 levels, and the median IL-8 level here was 3.86 pg/mL (range, 1.42-11.60 pg/mL). A significant correlation was observed between plasma levels of IL-6 and IL-8 (Spearman r = 0.4810, p-value <0.0001), and the levels of both cytokines correlated positively with age and β2-microglobulin. There was also a trend between cytokine levels and RAI stage. There was no correlation between cytokine levels and CD38, IgVH mutation status or the Zap-70 level. For patients aged ≥65 yrs, approximately 22% had increased levels of plasma IL-6 (>3 pg/mL, 8% in normals) and 25% had increased IL-8 (>10 pg/mL, 8% in normals). Plasma from CLL patients with high IL-6 levels was able to induce IL-6 expression in CLL cells whereas plasma from CLL patients with low IL-6 levels failed to induce IL-6 expression in CLL cells. This indicates that factor(s) within the microenvironment are contributing to increased IL-6 levels in CLL. We have previously shown that the relative survival decreases in CLL after age 65 yrs. The present study suggests that this may be related to a potentiation in the age-related increase in IL-6/IL-8 that is observed in the normal population. Whether the increase in mortality in elderly CLL patients is related to frailty/cardiovascular disease or to CLL progression is being investigated. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1762.