The effect of prostaglandin E2 and indomethacin on the cytotoxic response to mycobacterial antigens.
The effect of prostaglandin E2 and indomethacin on the generation of cytotoxic T-lymphocytes in response to Mycobacterium tuberculosis (MTB) antigens was compared between healthy controls and rheumatoid arthritis patients. Peripheral blood mononuclear cells (PBMC) from 16 healthy individuals and 15 RA patients were stimulated for 7 days with an irradiated, sonicated preparation of MTB in the presence or absence of PGE2 or indomethacin and assayed for cytotoxic activity on autologous target cells prepulsed with MTB. The mean cytotoxic activity generated was lower in patients than in controls. Exogenous PGE2 suppressed the cytotoxicity directed against MTB pulsed targets in 12 of 16 controls, but in only 1 of 11 patients. Indomethacin enhanced this cytotoxicity in only 2 of 16 controls but in 6 of 10 RA patients. When effector cells were derived from the synovial fluid, PGE2 again had no effect and indomethacin enhanced the cytotoxicity. Our data suggest that the depressed cytotoxic response of RA patients to MTB may be due to the production of endogenous PGE2. Cyclooxygenase inhibitors commonly used in the treatment of RA may influence MTB induced cytotoxicity in patients. In addition to their anti-inflammatory effects within the joint, non-steroidal anti-inflammatory drugs may potentially enhance cytotoxic reactions which are induced by antigens, such as MTB cross-reactive heat shock proteins.
Yuan
S
S
Department of Molecular Medicine, School of Medicine, University of Auckland, New Zealand.
Tan
P L
PL
Skinner
M A
MA
D000942:Antigens, Bacterial / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D009169:Mycobacterium tuberculosis / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology
D000942:Antigens, Bacterial; D015232:Dinoprostone; D007213:Indomethacin