Potentiation of Nonspecific Immunotherapy of Experimental Lung Metastases by Indomethacin
- 1 January 1983
- journal article
- research article
- Published by Informa UK Limited in Journal of Immunopharmacology
- Vol. 5 (4), 277-290
- https://doi.org/10.3109/08923978309026449
Abstract
Intraperitoneal treatment with the interferon inducer, maleic anhydride-divinyl ether copolymer (MVE), has previously been demonstrated to effectively reduce metastatic growth in the lungs and prolong survival times of BALB/c mice bearing the syngeneic Madison lung (M109) carcinoma. Resistance to lung metastasis formation induced by MVE appears to result from an activation of alveolar macrophage function. Since E-type prostaglandins (PGE) suppress the cytotoxic activity of activated macrophages, we sought to determine the effect of indomethacin, a prostaglandin synthetase inhibitor, on the antimetastatic activity of MVE. An artificial metastasis model was developed in which single-cell suspensions of the M109 tumor were injected i.v. into BALB/c mice. A 52,600 molecular weight fraction of MVE (MVE-5) was administered i.p. at 20 mg/kg two days prior to tumor inoculation. MVE-5 treatment produced >80 percent reduction in macroscopic lung lesion formation at Day 15 and Day 19 after tumor inoculation and a resultant 45 percent increase in lifespan. Chronic administration of indomethacin in the drinking water at 10 μg/ml potentiated the MVE-5 antitumor induced macrophage activation in vivo. In the absence of any evidence for an interaction between indomethacin and circulating M109 cells, it was felt that the potentiating effect could be best explained in terms of interference with PGE-mediated feedback inhibition of macrophage functional activity.This publication has 18 references indexed in Scilit:
- Relationship of the suppression of macrophage mediated tumor cytotoxicity in conjunction with secretion of prostaglandin from the macrophages of breast cancer patientsInternational Journal of Immunopharmacology, 1982
- A mouse model for immunotherapy of osteosarcomaCancer Immunology, Immunotherapy, 1980
- Mechanism of action of mouse macrophages as antitumor effector cells: Role of arginaseCellular Immunology, 1980
- E-type prostaglandins and interferons: Yin-yang modulation of macrophage tumoricidal activityMedical Hypotheses, 1980
- Rat alveolar macrophages are susceptible to activation by free and liposome-encapsulated lymphokines.The Journal of Immunology, 1980
- Increased Prostaglandin Synthesis by Macrophages from Tumor-Bearing MiceThe Journal of Immunology, 1979
- Regulation of Macrophage Tumoricidal Function: A Role for Prostaglandins of the E SeriesScience, 1978
- Mechanism of inhibition of tumour growth by aspirin and indomethacinBritish Journal of Cancer, 1978
- Prostaglandin E production by human blood monocytes and mouse peritoneal macrophages.The Journal of Experimental Medicine, 1978
- Stimulation of prostaglandin E production in cultured human fibroblasts by poly(I) · poly(C) and human interferonNature, 1977