The effects of sulphasalazine and its metabolites on prostaglandin production by human mononuclear cells.
Although it has been proposed that sulphasalazine (SASP) and its metabolite 5-aminosalicylic acid (5-ASA) act therapeutically by inhibiting production of vasoactive and immunoregulatory prostaglandins (PGs), in previous in vitro studies these drugs have both inhibited and promoted PG production. This study demonstrates that SASP and 5-ASA promote or inhibit peripheral blood mononuclear cell PG production depending upon the PG measured, the concentration of the drug, and whether the cells were stimulated. Sulphapyridine, the other constituent of SASP, only inhibited production. At high concentrations of SASP and 5-ASA the viability of mononuclear cells was reduced. The enhancement of PG production and toxicity was greater with SASP than 5-ASA, while the PGs most affected by SASP were not those most affected by 5-ASA. Thus, in vitro SASP may possess properties other than those of 5-ASA and this may explain the different therapeutic properties of these two compounds.
Punchard
N A
NA
Gastrointestinal Laboratory, Rayne Institute, St Thomas' Hospital, London, U.K.
Boswell
D J
DJ
Greenfield
S M
SM
Thompson
R P
RP
D000636:Aminosalicylic Acids / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008070:Lipopolysaccharides; D008297:Male; D019804:Mesalamine; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D012460:Sulfasalazine / Q000378:metabolism / Q000494:pharmacology*
D000636:Aminosalicylic Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D011453:Prostaglandins; D012460:Sulfasalazine; D019804:Mesalamine