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Mediators of Inflammation
Volume 8 (1999), Issue 4-5, Pages 253-259
http://dx.doi.org/10.1080/09629359990423

Cyclosporin A Decreases Human Macrophage Interleukin-6 Synthesis at Post-Transcriptional Level

1Area de Medicina. Fundación Hospital de Alcorcón, Spain
2Departmento de Fisiología. Universidad de Salamanca, Spain
3Centro de Salud Miguel Servet. Alcorcón, Spain
4Hospital General de Albacete, Spain
5Departmento de Medicina. Universidad de Salamanca, Spain
6Departamento de Ciencias Clínicas. Universidad de Las Palmas, Spain
7Internal Medicine Unit, Fundación Hospital de Alcorcón, Budapest 1, Alcorcón, Madrid 28922, Spain

Copyright © 1999 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

In addition to its well-established effect on T cells, cyclosporin A (CsA) also inhibits inflammatory cytokine production by macrophages. However, little is known about the mechanism of action of CsA on macrophage cytokine production. We measured the effect of CsA on basal and phorbol-myristate-acetate (PMA)-stimulated production of interleukin-6 using the human monocyte cell line U937 differentiated with dimethylsulfoxide (DMSO). Interleukin-6 levels were measured in supernatant and cell lysates using specific enzyme-linked immunosorbent assays. We found that CsA decreases not only IL-6 release but also cytokine synthesis. The concentration of CsA used did not affect either cell viability or proliferation. Three possibilities may be advanced to explain the CsA-due decrease in IL-6 production by macrophages: (a) inhibition of the synthesis of an early common regulatory protein, (b) inhibition of cytokine gene transcription, or (c) modulation of post-transcriptional events. The first possibility was tested by measuring the effect of cycloheximide on the experimental system during the first 3 hours of culture. Although cycloheximide decreased total cytokine synthesis, the pattern of cytokine modulation by CsA persisted. These data suggest that CsA-mediated macrophage cytokine inhibition is not mediated by an early common regulatory protein. To further explore the inhibition mechanism, we measured IL-6 mRNA levels by Northern blot. IL-6 mRNA levels were unaffected by CsA both in resting and PMA-stimulated cells. We conclude that in human macrophages CsA diminishes IL-6 production at post-transcriptional level.