British Journal of Rheumatology 1990;29:358-362 THE INHIBITION OF NK CELL FUNCTION BY AZATHIOPRINE DURING THE TREATMENT OF PATIENTS WITH RHEUMATOID ARTHRITIS

Treatment with azathioprine of patients with rheumatoid arthritis leads to a dramatic reduction in the 4 h NK cytotoxicity against K562 cells. The 24 h cytotoxicity against K562 and U937 cells, however, remains intact. The generation of cell-free supernatant cytotoxic factor(s) after incubating non-adherent mononuclear cells with U937 cells for 24 h is similar in the azathioprine patients and the controls. A large part of this supernatant cytotoxicity is due to tumour necrosis factor a which can be inhibited by a specific monoclonal antibody. The mechanism of the reduced 4 h NK cytotoxicity remains unknown but is probably not related to the anti-inflammatory properties of azathioprine. KEY WORDS: Cytotoxicity, Tumour necrosis factor a, Rheumatoid arthritis, Azathioprine. NATURAL killer (NK) cells are well characterized effec-tor cells with multiple functions including cytotoxicity, interferon production and immunoregulation. Cyto-toxicity is due to a direct cell-cell lysis as well as the release of soluble factors [1]. NK cells are able to recognize, bind and lyse specific target cells. Target cell contact is a necessary but not sufficient condition for lysis. Target cell binding an