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© 1988 British Society for Rheumatology

research-article

EFFECT OF SULPHASALAZINE AND ITS METABOLITES ON MITOGEN INDUCED TRANSFORMATION OF LYMPHOCYTES—CLUES TO ITS CLINICAL ACTION?

P. SHELDON, C. WEBB and K. A. GRINDULIS*

Department of Microbiology Medical Sciences Building, University Road, Leicester LE1 7RH, UK
*Sandwell District General Hospital W. Midlands B71 4HJ, UK

The effects of sulphasalazine (SASP), sulphapyridinc (SP), and 5-aminosalicylic acid (5-ASA) have been studied on mouse spleen cells cultured in the presence of phytohaemagglutmin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM) and lipopolysaccharide (LPS).

SASP exhibited a significant degree of suppression, at doses in the range 25–100 .µg/ml (p < 0.01), this suppression being >50% at 50 µg/ml. SP exhibited only a minor degree of suppression (10% at 75 µg/ml. p < 0.01). Coadministration of a non-steroidal anti-inflammatory drug (NSAID), indomethacin, produced no evidence of further suppression in the presence of SASP or SP. Administration of SP plus 5-ASA to parallel cultures that were profoundly suppressed by the molecular equivalent amount of SASP resulted in no suppression. This implied requirement of the intact parent molecule (SASP) to produce this effect, at these concentrations.

The concentration of SASP required to produce more than 50% suppression was higher than that ever attained in the peripheral blood of humans receiving therapeutic doses of the drug. Human lymphocytes are similarly suppressed by SASP, but only at higher concentrations than are required for murine cells. Thus, if the parent drug is the active moiety and requires these concentrations to be effective in vivo, it follows that the site where these effects may be mediated is likely to be the intestinal tract. The effects described would suggest the gut associated lymphoid tissue as a likely target.

KEY WORDS: 5-Aminosalicylic acid, Small intestine, Rheumatoid arthritis, Reactive arthritis, Ankylosing spondylitis


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