Indomethacin augments lymphokine-activated killer cell generation by patients with malignant mesothelioma

• Published in: Clinical immunology and immunopathology Vol. 53; no. 1; pp. 68 - 77
• Main Authors: Manning, Linda S., Bowman, Rayleen V., Davis, Mark R., Musk, Arthur W., Robinson, Bruce W.S.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.10.1989; New York, NY Academic Press; Boston
• Subjects: 560300 - Chemicals Metabolism & Toxicology; ANIMAL CELLS; ANIMALS; ANTIPYRETICS; ASBESTOS; Asbestos - adverse effects; Biological and medical sciences; BIOLOGICAL FUNCTIONS; BIOLOGICAL MATERIALS; BLOOD; BLOOD CELLS; BODY FLUIDS; CELL PROLIFERATION; CENTRAL NERVOUS SYSTEM DEPRESSANTS; CONNECTIVE TISSUE CELLS; Cytotoxicity, Immunologic - drug effects; DISEASES; Drug Synergism; DRUGS; Environmental Exposure; ENZYME INHIBITORS; FUNCTIONS; GROWTH FACTORS; Humans; IMMUNOSUPPRESSION; Indomethacin - pharmacology; Interleukin-2 - pharmacology; Killer Cells, Natural - drug effects; Killer Cells, Natural - immunology; LEUKOCYTES; LYMPHOCYTES; LYMPHOKINES; LYSIS; MAMMALS; MAN; MATERIALS; Medical sciences; MEMBRANES; Mesothelioma - etiology; Mesothelioma - immunology; Mesothelioma - pathology; MITOGENS; NEOPLASMS; OCCUPATIONAL DISEASES; Occupational Diseases - immunology; Occupational Diseases - pathology; OCCUPATIONAL EXPOSURE; ORGANIC COMPOUNDS; PATIENTS; PLEURA; Pleural Neoplasms - etiology; Pleural Neoplasms - immunology; Pleural Neoplasms - pathology; Pneumology; PRIMATES; PROSTAGLANDINS; Prostaglandins - biosynthesis; PROTEINS; RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT; SEROUS MEMBRANES; SOMATIC CELLS; TOXICITY; TUMOR CELLS; Tumor Cells, Cultured; Tumors of the respiratory system and mediastinum; VERTEBRATES; Human; Biological properties; Cytolysis; Respiratory disease; Cytotoxicity test; Stimulation; Non steroidal antiinflammatory agent; Malignant mesothelioma; LAK cell; Tumor; Target cell; Tumor cell; Pleura
• ISSN: 0090-1229; 1090-2341
• DOI: 10.1016/0090-1229(89)90102-5

Human malignant mesothelioma (MM) cells are resistant to natural killer (NK) cell lysis but susceptible to lysis by lymphokine-activated killer (LAK) cells from control individuals. The present study was performed to determine the capacity of patients with MM ( n = 22) and individuals occupationally exposed to asbestos (the major population at risk of developing this disease, n = 52) to generate LAK cells capable of effectively lysing human mesothelioma cells. Compared to controls ( n = 20), both patient groups demonstrated significantly depressed LAK cell activity against mesothelioma tumor cell targets (55 ± 3% lysis by controls vs 34 ± 3% lysis by patients with MM, P < 0.005; and 45 ± 3% lysis by asbestos-exposed individuals, P < 0.025). Addition of 10 μg/ml indomethacin during LAK cell generation restored normal LAK cell activity for patients with MM (52 ± 6% lysis of cultured human MM cells, P = NS compared to controls), suggesting that the defective cytolytic cell function observed in some patients with MM is a result of prostaglandin-induced immunosuppression. The ability of indomethacin to restore suppressed LAK cell activity in patients with MM suggests that the concomitant use of this agent in ex vivo LAK cell generation and in patients undergoing interleukin/LAK cell therapy may be beneficial.