[Potent effects of the prostaglandin synthesis inhibitor indomethacin on the cellular immune response in gastrointestinal cancer patients].
An increased level of prostaglandin E2, which is produced in carcinoma tissue, has been suggested to be involved in immunosuppression in cancer patients. This study examines the hypothesis in which the inhibition of prostaglandin production by a nonsteroidal anti-inflammatory agent, indomethacin, could modulate cancer-induced cellular immunosuppression. The experimental results demonstrated (i) a restoration of cellular immune reaction (NK activity of spleen monocytes) followed by tumor regression in subcutaneously transplanted colon adenocarcinoma 26-bearing BALB/c mice, which received 0.002% water solution as drinking water from day 0 or 7 of tumor transplantation, compared with indomethacin-untreated mice, (ii) an improved cellular immune response (PHA-and Con A-augmented lymphocyte blastogenesis, NK activity and LAK activity of peripheral venous blood monocytes) in 19 stomach cancer and 11 colorectal cancer patients before surgery, who received a daily oral dose of 75 mg indomethacin for 7 days, and in 8 colorectal cancer patients after curative surgery, who received a daily oral dose of 600 mg tegafur and 50 mg indomethacin for 1 month or longer, compared to patients without indomethacin treatment. It suggests, therefore, that the prostaglandin synthesis inhibitor, indomethacin, may restore cellular immunity, and may provide a good therapeutic tool against cancer of the gastrointestinal tract.
Koyama
H
H
Narisawa
T
T
Kodama
M
M
Ishikawa
K
K
Kusaka
H
H
Yamazaki
Y
Y
Koyama
K
K
D000818:Animals; D003131:Combined Modality Therapy; D005770:Gastrointestinal Neoplasms / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D007213:Indomethacin / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011453:Prostaglandins / Q000096:biosynthesis*
D011453:Prostaglandins; D007213:Indomethacin