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Serum YKL-40 and Interleukin 6 Levels in Hodgkin Lymphoma

Authors' Affiliations: ¹ Department of Epidemiology Research, State Serum Institute; ² Department of Rheumatology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark; ³ Clinical Epidemiology Unit, Department of Medicine, Karolinska University Hospital; ⁴ Departments of Medical Epidemiology and Biostatistics and ⁵ Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden; ⁶ Northern California Cancer Center, Fremont, California; ⁷ Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California; ⁸ Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts; ⁹ Department of Oncology, Radiology and Clinical Immunology, Uppsala University Hospital, Uppsala, Sweden; and ¹⁰ Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark

Requests for reprints: Robert J. Biggar, Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen, Denmark. Phone: 45-3268-3722; Fax: 45-3238-3165; E-mail: rjb{at}ssi.dk.

Purpose: Serum levels of the inflammatory markers YKL-40 and interleukin 6 (IL-6) are increased in many conditions, including cancers. We examined serum YKL-40 and IL-6 levels in patients with Hodgkin lymphoma, a tumor with strong immunologic reaction to relatively few tumor cells, especially in nodular sclerosis Hodgkin lymphoma.

Experimental Design: We analyzed Danish and Swedish patients with incident Hodgkin lymphoma (N = 470) and population controls from Denmark (n = 245 for YKL-40; n = 348 for IL-6). Serum YKL-40 and IL-6 levels were determined by ELISA, and log-transformed data were analyzed by linear regression, adjusting for age and sex.

Results: Serum levels of YKL-40 and IL-6 increased in Hodgkin lymphoma patients compared with controls (YKL-40, 3.6-fold; IL-6, 8.3-fold; both, P < 0.0001). In pretreatment samples from pretreatment Hodgkin lymphoma patients (n = 176), levels were correlated with more advanced stages (P_trend, 0.0001 for YKL-40 and 0.013 for IL-6) and in those with B symptoms; however, levels were similar in nodular sclerosis and mixed cellularity subtypes, by EBV status, and in younger (<45 years old) and older patients. Patients tested soon after treatment onset had significantly lower levels than pretreatment patients; however, even 6 months after treatment onset, serum YKL-40 and IL-6 levels remained significantly increased compared with controls. In patients who died (n = 12), pretreatment levels for YKL-40 and IL-6 were higher than in survivors, although not statistically significantly.

Conclusions: Serum YKL-40 and IL-6 levels were increased in untreated Hodgkin lymphoma patients and those with more advanced stages but did not differ significantly by Hodgkin lymphoma histology. Following treatment, serum levels were significantly lower.