Inhibition of cell mediated cytotoxicity by sulphasalazine: effect of in vivo treatment with 5-aminosalicylic acid and sulphasalazine on in vitro natural killer cell activity

Decreased cell mediated cytotoxicity occurs frequently in inflammatory bowel disease, particularly in patients with active disease. It is not clear, however, whether this decrease is caused by the disease or is a consequence of the medical treatment. In this study we evaluated the effect of in vivo treatment with 5-aminosalicylic acid and sulphasalazine on the in vitro natural killer cell activity in five patients with inflammatory bowel disease in remission and in four healthy control subjects in a double blind randomised crossover trial preceded and separated by four weeks of treatment with placebo. The natural killer cell activity was significantly impaired in 67% (six of nine subjects) after four weeks' sulphasalazine treatment and tended to be related to subjects with a slow acetylator phenotype. In contrast, 5-aminosalicylic acid treatment caused only a marginal reaction in the natural killer cell activity in 22% (two of nine subjects). The inhibitory effects were found to be reversible since the decreased natural killer cell activity was completely restored after placebo treatment in all subjects. In conclusion, in vivo treatment with sulphasalazine inhibits the in vitro natural killer cell activity and this seems to be mediated by the sulphapyridine moiety. This phenomenon may contribute to the low natural killer cell activity found in patients with active inflammatory bowel disease.