Enhanced production of interleukin 6 in peripheral blood monocytes stimulated with mucins secreted into the bloodstream.
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.
Yokoigawa
Norio
N
Department of Surgery, Kansai Medical University, Moriguchi, Osaka, Japan.
Takeuchi
Noriko
N
Toda
Munetoyo
M
Inoue
Mizue
M
Kaibori
Masaki
M
Yanagida
Hidesuke
H
Tanaka
Hironori
H
Ogura
Tokuhiro
T
Takada
Hideho
H
Okumura
Tadayoshi
T
Kwon
A-H
AH
Kamiyama
Yasuo
Y
Nakada
Hiroshi
H
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
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