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Enhanced Production of Interleukin 6 in Peripheral Blood Monocytes Stimulated with Mucins Secreted into the Bloodstream

Authors' Affiliations: Departments of ¹ Surgery and ² Medical Chemistry, Kansai Medical University, Moriguchi, Osaka, Japan; ³ Department of Biotechnology, Faculty of Engineering, Kyoto Sangyo University, Kita-ku, Kyoto, Japan; and ⁴ Core Research for Educational Science and Technology Project, Japan Science and Technology Agency, Kawaguchi, Japan

Requests for reprints: Hiroshi Nakada, Department of Biotechnology, Faculty of Engineering, Kyoto Sangyo University, Kita-ku, Kyoto 630-8555, Japan. Phone: 75-705-1897; Fax: 75-705-1888; E-mail: hnakada{at}cc.kyoto-su.ac.jp.

Purpose: It has been reported that tumor progression is correlated with the serum level of interleukin 6 (IL-6). The purpose of this study was to investigate by what mechanism, other than production from tumor cell, the serum level of IL-6 is elevated in the tumor-bearing state.

Experimental Design: Monocytes from healthy donors were cultured in the presence of sera from colon cancer patients, and the activity to elevate IL-6 production was estimated. This activity of serum was also examined after various biochemical treatments.

Results: When monocytes from healthy donors were cultured in the presence of sera from patients with colon cancer, secretion of IL-6 from the cells was markedly elevated. Serum proteins were fractionated on Sepharose 4B and the activity to elevate IL-6 production was found in the excluded fractions. Sialyl Tn antigen was detected in these same fractions. By excluding some mucins from the serum, the inducing activity was reduced to 40% of the original level. Furthermore, we purified mucins from the conditioned medium of colon cancer cells. Production of IL-6 was effectively elevated by a small amount of purified mucins in a dose-dependent manner. When the inducing activity was examined in the presence of binding or competitive inhibitors to the scavenger receptor, the effect was remarkably reduced.

Conclusions: Mucins secreted from colon cancer cells into the bloodstream induce production of IL-6 in peripheral blood monocytes through the scavenger receptor, which may be responsible for the high level of serum IL-6 in colon cancer patients.