title: Enhanced production of interleukin 6 in peripheral blood monocytes stimulated with mucins secreted into the bloodstream.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Surgery, Kansai Medical University, Moriguchi, Osaka, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Yokoigawa
authors.forename: Noriko
authors.initials: N
authors.lastname: Takeuchi
authors.forename: Munetoyo
authors.initials: M
authors.lastname: Toda
authors.forename: Mizue
authors.initials: M
authors.lastname: Inoue
authors.forename: Masaki
authors.initials: M
authors.lastname: Kaibori
authors.forename: Hidesuke
authors.initials: H
authors.lastname: Yanagida
authors.forename: Hironori
authors.initials: H
authors.lastname: Tanaka
authors.forename: Tokuhiro
authors.initials: T
authors.lastname: Ogura
authors.forename: Hideho
authors.initials: H
authors.lastname: Takada
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Okumura
authors.forename: A-H
authors.initials: AH
authors.lastname: Kwon
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kamiyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakada
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism*; D018929:Cell Culture Techniques; D003110:Colonic Neoplasms / Q000097:blood*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D009077:Mucins / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051116:Receptors, Scavenger; D015854:Up-Regulation
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D017077:Culture Media, Conditioned; D015850:Interleukin-6; D009077:Mucins; D010446:Peptide Fragments; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; C055491:sialosyl-Tn antigen