Imbalance of Pro- and Anti-Inflammatory Cytokines in Patients With cHL Persists Despite Treatment Compared With Control Subjects

Author(s)

da Silva, Priscilla Brito ; Perini, Guilherme Fleury ; Pereira, Luciana de Andrade ; Sacconato, Elyse Moritz ; Damasco Penna, Adriana Marques ; Garibaldi, Joao ; Cavalcante, Egyla ; Baiocchi, Otavio C. G.

• Document type: Journal article
• Source: CLINICAL LYMPHOMA MYELOMA & LEUKEMIA; v. 15, p. 7-pg., 2015-06-01.

Abstract

To evaluate the importance of immune alterations that contribute for the escape of HRS neoplastic cells, we analysed serum levels of cytokines in 29 pacients with cHL before and after treatment and compared with healthy subjects. At diagnosis, higher levels of IL-6, IL-10, TNF-alpha and sCD25 were observed when compared with healthy subjects. After treatment, levels of IL-6, IL-10 and sCD25 had a important reduction but not to normal levels. Elevated levels of IL-6 were correlated with higher IPS, elevated levels of sCD25 with low serum albumin and elevated leveles of IFN-gamma with B symptoms. Background: Classical Hodgkin lymphoma (cHL) is a malignant lymphoma that most commonly affects young adults. The lymphomagenesis of cHL depends largely on immune alterations that contribute to proliferation and maintenance of the Hodgkin-Reed-Sternberg (HRS) neoplastic cells. A combination of different immune processes is responsible for the escape of HRS cells, the imbalance between pro- and anti-inflammatory cytokines being one of them. In this study, we aimed to measure serum levels of pro- and anti-inflammatory cytokines in cHL patients before and after treatment compared with a healthy controls group, and to investigate associations with clinical and pathologic characteristics. Patients and Methods: We prospectively studied all cases of cHL diagnosed between March 2009 to March 2013 at the Universidade Federal de Sao Paulo and Hospital Santa Marcelina, in Sao Paulo, Brazil. Twenty-nine cases with sufficient clinical data were included in this study. Additionally, 18 healthy control subjects were included and recruited from our University Blood Bank. Serum cytokine levels of interleukin (IL)-2, IL-4, IL-5, IL-6, IL-10, IL-17, tumor necrosis factor (TNF)-alpha, soluble IL-2 receptor (sCD25), vascular endothelial growth factor (VEGF), and interferon (IFN)-gamma were determined in serum of patients and controls using a multiplexed immunoassay system. Results: Higher International Prognostic Score was positively correlated with increased levels of IL-6 (P = .003); sCD25 levels were higher in patients with low serum albumin (P = .04), and IFN-gamma seemed to correlate with B symptoms, although did not reach statistical significance (P = .057). Pretreatment levels of IL-10, IL-6, TNF-alpha, and sCD25 were increased in cHL patients compared with in healthy control subjects (P < .001), with median values of 7 pg/mL (range, 0.3-230.9), 5.3 pg/mL (range, 0.4-72.7), 14.6 (range, 4.0-60.4), and 575.9 pg/mL (range, 7.5-1813.3), respectively. Treatment significantly reduced levels of IL-10 (7.0 to 0.3; P < .001), IL-6 (5.3 to 0.4; P = .014), and sCD25 (575.9 to 93.5; P < .001), however, levels of IL-4 increased (0.6 to 2.2; P = .002). Compared with normal control subjects, increased levels of IL-6 (0.4 to 0.4; P = .027), sCD25 (93.5 to 7.5; P = .002), and TNF-alpha (12 to 8.7; P = .003) persisted after treatment. Conclusion: In this study we showed higher levels of IL-6, IL-10, TNF-alpha, and sCD25 in cHL patients at diagnosis than in healthy control subjects. After treatment, levels of IL-6, IL-10, and sCD25 decreased gradually but did not normalize. Understanding the cytokine pattern is extremely important in the development of future therapies that target interactions between neoplastic cells and the inflammatory microenvironment. (C) 2015 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 12/16864-1 - Evaluation of regulatory and Th17 lymphocytes and its correlation with pro and antiinflammatory citoquines in patients with Classical Hodgkin lymphoma
• Grantee: Otavio Cesar Carvalho Guimarães Baiocchi
• Support Opportunities: Regular Research Grants