The effects of thiol compounds on mononuclear cell functions in arthritic rats.

  • S. F. Chai

Student thesis: Doctoral ThesisPhD

Abstract

Levels of free SH groups are depressed in the sera of patients with rheumatoid arthritis (RA) especially during active disease. However, the immunopathological significance of this effect is uncertain. Using adjuvant arthritis (AA) as a model of RA, the changes in serum protein SH level and reactivity during the course of AA were studied using a spectrophotometric method. A major depression of serum SH level and reactivity was found in arthritic rats and this was associated with persistent inflammatory phase of disease. This depression may be caused by oxidative stress due to production of oxidative species by activated phagocytes. In vivo D-penicillamine treatment of AA rats increased both serum SH level of reactivity towards normal values over days 14-21. This result suggests that D-pencillamine may act as a reducing agent, restoring the free SH groups that have been oxidised (blocked) in active AA. Rat mononuclear cell proliferation to the mitogen ConA was stimulated by the addition of 2-mercaptoethanol (2-ME) to the cultures. This ConA response was completely inhibited by the cell surface SH blocking agent, PHMPSA. During the course of AA in Sprague-Dawley rats, spleen (SC) and lymph node cells (LNC) responded poorly in vitro to ConA. The addition of 2-ME was found to reverse and enhance this depressed ConA response. D-penicillamine in vivo also modified the pattern of ConA stimulated proliferative response of AA rat SC and LNC, converting the markedly inhibited response to ConA at day 14 to an enhanced response when compared with cultures from untreated arthritic rats and nonarthritic rats. These results indicate that cell surface thiols are necessary for the proliferation of rat SC and LNC and that the altered cell function in AA may be due, at least in part, to blockade of the functional free cell surface SH groups. 2-ME in vitro and D-penicillamine in vivo could help to maintain cell surface SH groups in a reduced state. Alternatively, the depressed response could be attributed to suppression from activated macrophages via a mechanism involving SH groups. The depressed immune response in AA was not due to prostaglandin synthesis by activated macrophages nor was it due to an impaired synthesis of interleukins. Increased amounts of IL-1 were produced by AA rat peritoneal macrophages and SC from these animals produced slightly reduced amounts of IL-2. D-penicillamine treatment decreased the synthesis of IL-1 but had no effect on IL-2 production. The synthesis of these interleukins was not SH dependent as 2-ME and PHMPSA had no effect. Although D-penicillamine treatment in vivo leads to dramatic changes in certain mononuclear cell (MNC) functions, it has no effect on the clinical course of AA. The significance of altered MNC activity in the pathogenesis of AA is therefore questionable and the usefulness of AA as a model for detecting novel antirheumatic drugs with immunoregulatory actions is limited.
Date of Award1985
Original languageEnglish
Awarding Institution
  • University of Bath

Cite this

The effects of thiol compounds on mononuclear cell functions in arthritic rats.
Chai, S. F. (Author). 1985

Student thesis: Doctoral ThesisPhD