title: Imbalance of Pro- and Anti-Inflammatory Cytokines in Patients With cHL Persists Despite Treatment Compared With Control Subjects.
abstract: 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.
  
  
  METHODS
  We prospectively studied all cases of cHL diagnosed between March 2009 to March 2013 at the Universidade Federal de São 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)-α, soluble IL-2 receptor (sCD25), vascular endothelial growth factor (VEGF), and interferon (IFN)-γ 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-γ seemed to correlate with B symptoms, although did not reach statistical significance (P = .057). Pretreatment levels of IL-10, IL-6, TNF-α, 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-α (12 to 8.7; P = .003) persisted after treatment.
  
  
  CONCLUSIONS
  In this study we showed higher levels of IL-6, IL-10, TNF-α, 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.
authors: Departamento de Oncologia Clínica e Experimental, Universidade Federal de São Paulo, UNIFESP, São Paulo, São Paulo, Brazil.
authors: Priscilla Brito
authors: PB
authors: da Silva
authors: Departamento de Oncologia Clínica e Experimental, Universidade Federal de São Paulo, UNIFESP, São Paulo, São Paulo, Brazil.
authors: Guilherme Fleury
authors: GF
authors: Perini
authors: Departamento de Oncologia Clínica e Experimental, Universidade Federal de São Paulo, UNIFESP, São Paulo, São Paulo, Brazil.
authors: Luciana de Andrade
authors: Lde A
authors: Pereira
authors: Departamento de Oncologia Clínica e Experimental, Universidade Federal de São Paulo, UNIFESP, São Paulo, São Paulo, Brazil.
authors: Elyse Moritz
authors: EM
authors: Sacconato
authors: Departamento de Oncologia Clínica e Experimental, Universidade Federal de São Paulo, UNIFESP, São Paulo, São Paulo, Brazil.
authors: Adriana Marques Damasco
authors: AM
authors: Penna
authors: Departamento de Oncologia Clínica e Experimental, Universidade Federal de São Paulo, UNIFESP, São Paulo, São Paulo, Brazil.
authors: Joao
authors: J
authors: Garibaldi
authors: Departamento de Oncologia Clínica e Experimental, Universidade Federal de São Paulo, UNIFESP, São Paulo, São Paulo, Brazil.
authors: Egyla
authors: E
authors: Cavalcante
authors: Departamento de Oncologia Clínica e Experimental, Universidade Federal de São Paulo, UNIFESP, São Paulo, São Paulo, Brazil. Electronic address: baiocchi@unifesp.br.
authors: Otavio C G
authors: OC
authors: Baiocchi
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006689:Hodgkin Disease / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines
keywords: Hodgkin lymphoma; IL-10; IL-6; Treatment; sCD25