Please use this identifier to cite or link to this item:
Title: The effects of sulfasalazine, its metabolites and related compounds on mitogen-induced lymphocyte proliferation.
Authors: Webb, Christopher J. A. L. (Christopher John Anthony Luke)
Award date: 1992
Presented at: University of Leicester
Abstract: Salicylazosulfapyridine (SASP), used in the management of rheumatoid arthritis (RA), comprises sulfapyridine (SP) azo linked to 5-aminosalicylic acid (5-ASA). SASP inhibited mitogen-induced, human, and murine, T- and B-lymphocyte proliferation in vitro. Efficient suppression was attained at supra-physiological levels of SASP; equimolar SP was slightly inhibitory, 5-ASA, negligible. SASP-mediated suppression (SMS) was not due to cytotoxicity, nor to a concerted effect of SP and 5-ASA; the drug appeared to influence lymphocytes rather than macrophages. The action of SASP and various 5-ASA azo compounds on mouse splenocyte responses to Concanavalin A (Con A), were further analyzed. SMS was dependent on serum, and mitogen, concentrations, and cell numbers, in culture. SMS was abrogated by washing SASP-containing Con A cultures drug-free after 24 hours, perhaps suggesting that SASP interferes with a cellular signal effecting the transition of lymphocytes from G1 to S phase. Interleukin-2 (IL-2) failed to reverse SMS, possibly implying that SASP impedes the binding of IL-2 to its cellular receptor, a mechanism which may be germane to its therapeutic activity in RA. All SASP analogues tested were much weaker suppressants than SASP; olsalazine (two azo-linked 5-ASA molecules) was the strongest, although its isomers containing 4-ASA were markedly less potent. It was inferred from the findings of several SASP analogue studies, that both the SP and 5-ASA groups within the intact SASP structure, were required for SMS. SMS of phytohaemagglutinin-induced RA lymphocyte proliferation in vitro, declined in clinical "responders", after 12 weeks of SASP therapy; this change in lymphocyte behaviour was absent in unresponsive RA patients. Possible explanations are discussed.
Level: Doctoral
Qualification: Ph.D.
Rights: Copyright © the author. All rights reserved.
Appears in Collections:Theses, Dept. of Biology
Leicester Theses

Files in This Item:
File Description SizeFormat 
U641594.pdf35.82 MBAdobe PDFView/Open

Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.