Increased levels of circulating interleukin‐6 in patients with hodgkin's disease

Abstract

Expression of interleukin-6 (IL-6) and IL-6 receptors has been demonstrated in Hodgkin and Reed-Sternberg (H and RS) cells in vitro and in vivo. In order to evaluate the clinical significance of IL-6 serum levels in patients with Hodgkin's disease (HD), we tested the sera of 56 untreated patients with HD by means of a sensitive sandwich ELISA. While IL-6 was only rarely detectable in healthy controls or patients with non-Hodgkin's lymphoma, 32 of 56 patients (57 per cent) had detectable IL-6 levels (range 12-32 pg/ml). The rates of detectable IL-6 levels and the median levels were not correlated with age, sex, histological subtype, stage or the presence of B-symptoms, nor with any of a wide spectrum of laboratory parameters tested, including erythrocyte sedimentation rate, total leukocyte and lymphocyte counts, serum levels of soluble CD8, CD25 or CD30. The rates of complete remissions and freedom from treatment failure were not different in IL-6-negative and IL-6-positive patients. Except in one of 23 follow-up sera taken after therapy, IL-6 was no longer detectable even for patients who suffered from progressing disease, suggesting that the neoplastic H and RS cells are not the major source of circulating IL-6.

Functional coexpression of Interleukin (IL)‐7 and its receptor (IL‐7R) on Hodgkin and Reed‐Sternberg cells: Involvement of IL‐7 in tumor cell growth and microenvironmental interactions of Hodgkin's lymphoma

“…42,43 IL-7R engagement on fibroblasts has been described to induce secretion of IL-6, 44 a cytokine potentially involved in H-RS cells growth and formation of the inflammatory infiltrate in HL. 1,2,[45][46][47] Consistent with this view, we have shown that engagement of IL-7R on HLFs determined a significant increase of IL-6 secretion from these cells. HL cell lines and primary H-RS cells produce IL-6, its levels being significantly higher in tissues from Epstein-Barr virus (EBV)-positive than EBV-negative cHL cases.…”

“…1 In addition, two separate studies documented the elevation of IL-6 serum levels in patients with HL, and correlated such abnormality with the presence of B-symptoms and impaired survival. [45][46][47][48] Our data, demonstrating that tumor cells-derived IL-7 may contribute to IL-6 secretion by HLFs and that HLFssecreted IL-7 stimulates tumor cell growth, highlight the complexity of cellular interactions underlying the biology of HL. [1][2][3][4][5][6][7] It cannot be excluded however, that different IL-7 producing or IL-7R expressing cell types, such as epithelial cells, macrophages or dendritic cells, and other microenvironmental cytokines (TNF-a, IL-1 or PDGF), 1 also contribute to IL-7/IL-6 crossregulation within the HL microenvironment.…”

Elevated Serum Levels of sCD30 and IL6 and Detectable IL10 Precede Classical Hodgkin Lymphoma Diagnosis

“…Primary HL tissue specimens express IL-6 (16), the question of whether IL-6 expression differs in EBV-positive compared with EBV-negative tumors remains unresolved (49–51). Several studies have reported higher serum IL-6 levels in pretreatment HL cases compared with controls (10, 23, 25–27). The findings of this study suggest that elevated IL-6 levels significantly predict future risk of both EBV-positive and EBV-negative cHL.…”

“…In addition, activated B cells that have undergone Ig class switching after stimulation by B-cell-stimulatory cytokines produce immunoglobulin E (IgE) (19). In serologic studies using samples obtained at or after diagnosis, but before initiation of treatment, cHL cases have often had elevated levels of sCD30 (20–22), IL-6 (23–28), IL-10 (28–30), and IgE (31, 32) compared with controls; however, the observed elevated levels may reflect existing disease.…”

Effect of IL‐6 promoter polymorphism on incidence and outcome in Hodgkin's lymphoma

“…IL‐6 is a pleiotropic cytokine with pro‐inflammatory, anti‐inflammatory and endocrine functions, which is induced by viral infections, lipopolysaccharides and a variety of cytokines (Van Snick, 1990). IL‐6 is only rarely detected in the serum of healthy individuals, but elevated levels have been detected in the serum of patients with HL (Gause et al , 1992) and have been associated with advanced disease and an unfavourable prognosis (Kurzrock et al , 1993). In a proportion of HL cases, the Epstein–Barr virus (EBV) is detectable and expressed in Hodgkin and Reed–Sternberg (HRS) cells and is thought to play a role in disease pathogenesis.…”