FK506 and Cyclosporin A Enhance IL-6 Production in Monocytes: A single-Cell Assay
The effect of FK506 and cyclosporin A (CsA) on the production of interleukin 6 (IL-6) in adherent monocytes was studied at a single-cell level by the avidinbiotin- peroxidase complex methods. The percentage of IL-6-producing monocytes increased when stimulated with lipopolysaccharide (LPS) at concen...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Hindawi Limited
1994-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/S0962935194000529 |
| Summary: | The effect of FK506 and cyclosporin A (CsA) on the production of
interleukin 6 (IL-6) in adherent monocytes was studied at a
single-cell level by the avidinbiotin- peroxidase complex methods.
The percentage of IL-6-producing monocytes increased when stimulated
with lipopolysaccharide (LPS) at concentrations between 10 ng/ml and
10 μg/ml, in a dose dependent manner. Both FK506 and CsA
enhanced the percentage of IL-6- producing monocytes stimulated with
100 pg/ml-1 μg/ml of LPS up to values near those
obtained with 10 μg/ml of LPS. The enhancement by FK506 and
CsA was not seen when monocytes were stimulated with a high
concentration of LPS (10 μg/ml). When monocytes were
stimulated with a low concentration of LPS (10 ng/ml), FK506 and
CsA enhanced IL-6 production in a dose dependent manner, at a drug
concentration of 0.12 nM–1.2 μM (0.1–1 000 ng/ml)
for FK506 and 0.83 nM–8.3 μM (1–10 000 ng/ml) for
CsA. The optimal effect of FK506 was achieved at a concentration
7-fold lower than that of CsA. In contrast, production of turnout
necrosis factor-α (TNFα and interleukin 1β
(IL-1β) was slightly suppressed by FK506 and CsA at the
concentrations tested. Moreover, pretreatment of monocytes with
FK506 and CsA had a significant enhancing effect on LPS-induced IL-6
production, while treatment with FK506 or CsA after LPS stimulation
had no effects on IL-6 production, suggesting that the enhancing
effect of each drug is exerted before LPS stimulation or at an early
stage of the post-receptor pathway after LPS stimulation. These
experiments demonstrate that FK506 and CsA can selectively enhance
IL-6 production in monocytes under certain conditions in
vitro and, possibly, also in vivo. |
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| ISSN: | 0962-9351 1466-1861 |