1,25-Dihydroxyvitamin D3 POtentiates the in vitro inhibitory effects of cyclosporin A on T cells from rheumatoid arthritis patients
✍ Scribed by Patrick Gepner; Bernard Amor; Catherine Fournier
- Publisher
- John Wiley and Sons
- Year
- 1989
- Tongue
- English
- Weight
- 558 KB
- Volume
- 32
- Category
- Article
- ISSN
- 0004-3591
No coin nor oath required. For personal study only.
✦ Synopsis
Treatment of rheumatoid arthritis (RA) with cyclosporin A (CsA) has been successful, but the adverse effects of the drug have limited its use. We investigated the capacity of another immunosuppressive agent, 1,25dihydroxyvitamin D, [1,25(OH),D,], to augment the effect of CsA on in vitro T cell functions. Exposure of CD4+ cells from RA patients or from normal subjects to either molecule alone resulted in a dose-dependent inhibition of phytohemagglutinin stimulation and interleukin-2 (IL-2) production that was more pronounced in cells from RA patients than in cells from normal subjects. Moreover, the action of CsA and 1,25(OH),D, on RA patient T cell functions in vitro was synergistic. Thus, in the presence of the vitamin D, metabolite, only one-hundredth the concentration of CsA was required to produce the same effect on IL-2 production as that produced by CsA alone. IL-2 receptor expression was also reduced by the addition of both drugs. In contrast, IL-1 production by RA monocytes was not affected by CsA and 1,25(OH),D3, either together or alone, and addition of IL-1 did not restore the ability of CD4+ cells from RA patients to secrete IL-2. Exogenous IL-2 reversed a large part of the inhibitory effect induced by both CsA and 1,25(OH),D3, indicating that the immunosuppressive properties of these agents are mediated From the INSERM U . 283 and the