Indomethacin augments lymphokine-activated killer cell generation by patients with malignant mesothelioma.
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 less than 0.005; and 45 +/- 3% lysis by asbestos-exposed individuals, P less than 0.025). Addition of 10 micrograms/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.
Manning
L S
LS
University Department of Medicine, Queen Elizabeth II Medical Centre, Nedlands, Western Australia.
Bowman
R V
RV
Davis
M R
MR
Musk
A W
AW
Robinson
B W
BW
D001194:Asbestos / Q000009:adverse effects*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004357:Drug Synergism; D004781:Environmental Exposure; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008654:Mesothelioma / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D009784:Occupational Diseases / Q000276:immunology* / Q000473:pathology; D010997:Pleural Neoplasms / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D011453:Prostaglandins / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D011453:Prostaglandins; D001194:Asbestos; D007213:Indomethacin