Soluble Cytokine Levels Correlate with the Activity and Clinical Stage of Hodgkin's Disease at Diagnosis

Abstract

The serum levels of some cytokines seem to correlate with outcome in Hodgkin's disease (HD) and may be helpful in formulating new and better prognostic systems. The aim of this study was to analyse the correlations between the serum levels of different cytokines and the clinico-hematological features suggestive of a worse prognosis. The study involved 31 pts with a "de novo" diagnosis of HD (median age: 30 yrs; M/F: 13/18; stage I/II vs III/IV: 19/12; B symptoms: 12; bulky disease and extranodal disease: 9). The serum levels of sCD30, TNFalpha, TNF receptor I and II, IL6, IL6 receptor, IL10, sICAM-1 were evaluated at diagnosis, and correlated with gender, age (< or =/> 30), stage (I-II vs III-IV), systemic symptoms, bulky disease, ESR (</> or = 40), serum copper (< or =/> 170 microg/dL), WBC counts (< or =/> 15x10(9)/L), prognostic scores (PS) according to Hasenclever (</> or = 2), and the presence of extranodal disease. Stages III/IV were associated with significantly higher levels of sCD30 and TNF-RI (p=0.03), systemic symptoms with significantly higher levels of sCD30, TNFalpha, IL6, TNF-RI (p=0.027, 0.03, 0.0005, 0.002), bulky disease with TNF-RI (p=0.03), high ESR with IL6 and TNF-RI (p=0.0011, 0.0001), high WBC counts with sCD30, IL6, TNF-RI (p=0.03, 0.002, 0.01), high serum copper with sCD30 and IL6 (p=0.05, 0.0004), higher PS with sCD30, IL6, TNF-RI (p=0.002, 0.0003, 0.005), extranodal disease with TNFalpha and IL6 (p=0.05, 0.01). It was possible to define cut-off levels for some cytokines (sCD30 > 33.15 U/mL, TNFalpha > 29.71 pg/mL, IL6 > 12.43 pg/mL, TNF-RI > 3.23 ng/mL, IL6-R > 57 ng/mL) that significantly correlate with systemic symptoms, higher disease stages, ESR, serum copper, WBC counts and PS. Our study shows that high sCD30, TNFalpha, IL6 and TNF-RI levels are associated with advanced disease or a worse prognostic score. In the context of multiparametric HD staging, cytokine evaluation may be useful for identifying candidates for more intensive therapies.

Patients above Sixty Years Lymphoma Treated with a New Strategy of Age with Hodgkin's

“…High TNF-levels predict myelosuppression in patients with lymphoma (26). High levels of TNF are also seen in patients with HL (27). The immune de ciency described in HL patients (28) combined with the myelosuppression caused by TNF might be extra deleterious in elderly HL patients.…”

Expression of the Tumor Necrosis Factor Receptor-Associated Factors (TRAFs) 1 and 2 is a Characteristic Feature of Hodgkin and Reed-Sternberg Cells

“…Thus, HRS cells may be capable of autoamplifying TNFR stimulatory signaling via autocrine and paracrine receptorligand interaction. Interestingly, a recent investigation of Vener and colleagues (41) not only demonstrated the presence of TNF-␣ and TNFRs in the majority of HD patients but also showed that levels of TNF-␣ and related cytokines correlate with disease activity and clinical stage in these patients. Investigation of the downstream intracellular mediators that direct TNFR signaling in HD, however, has been limited (37,38).…”

IL-6 levels and genotype are associated with risk of young adult Hodgkin lymphoma

“…33 Patients with untreated Hodgkin lymphoma have high levels of IL-6, 20,21 and these levels are correlated with presence of "B" symptoms (fever, night sweats), 34 stage, 22 and prognosis. 23,34 This evidence suggests a strong link between IL-6 and pathogenesis but not necessarily etiology. Our results suggest that the association may be causal, based on both the IL-6 genotype association and the phenotype difference in unaffected identical twins of case subjects (surrogate case subjects) compared with control subjects.…”

“…18 Reports suggest that the cytokine interleukin-6 (IL-6) may play an especially important role in pathogenesis because patients with untreated Hodgkin lymphoma have higher serum IL-6 levels than control subjects, [19][20][21] and IL-6 levels are correlated with prognosis. 22,23 However, it is unclear whether this is a predisease abnormality related to a specific susceptibility or part of the general pathogenic process.…”