Imperial College London
Alternate

Dr Paul Seldon

Central Faculty, Graduate School

Senior Teaching Fellow
 
 
 
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Contact

 

+44 (0)20 7594 5503p.seldon

 
 
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Location

 

3rd Floor off student hubSherfield BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Seldon:1998:10.1007/BF02737835,
author = {Seldon, PM and Barnes, PJ and Giembycz, MA},
doi = {10.1007/BF02737835},
journal = {Cell Biochem Biophys},
pages = {179--201},
title = {Interleukin-10 does not mediate the inhibitory effect of PDE-4 inhibitors and other cAMP-elevating drugs on lipopolysaccharide-induced tumors necrosis factor-alpha generation from human peripheral blood monocytes.},
url = {http://dx.doi.org/10.1007/BF02737835},
volume = {29},
year = {1998}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Lipopolysaccharide (LPS)-induced liver injury in mice and LPS-induced tumor necrosis factor-alpha (TNF-alpha) generation by murine macrophages and hepatocytes are suppressed markedly by agents that elevate intracellular cAMP. Phosphodiesterase (PDE)-4 inhibitors, beta 2-adrenoceptor agonists, and E-series prostaglandins also attenuate the induction of the TNF-alpha gene in human monocytes in response to bacterial LPS. The mechanism of action of cAMP is unclear, but in the mouse, is believed to involve the generation of this anti-inflammatory cytokine, interleukin-10 (IL-10). In this article, we describe the results of studies designed to determine the extent to which IL-10 contributes to the suppression of TNF-alpha generation from LPS-stimulated human monocytes evoked by 8-bromo cyclic AMP (8-Br-cAMP), rolipram, salbutamol, and prostaglandin E2 (PGE2). LPS evoked a time- and concentration-dependent generation of TNF-alpha (t1/2 = 4.5 h; EC50 = 273 pg/mL), which was inhibited by exogenous human recombinant (h) IL-10 (IC50 = 124 pg/mL), and by rolipram (EC50 = 420 nM), 8-Br-cAMP (EC50 = 77 (microM), PGE2 (EC50 = 15 nM) and salbutamol (EC50 = 20 nM). In addition, 8-Br-cAMP, PGE2; and salbutamol (but not rolipram) augmented significantly LPS-induced IL-10 production (two-to-fivefold) under identical experimental conditions. Pretreatment of monocytes with an anti-IL-10 monoclonal antibody (MAb) that abolished the inhibitory action of a maximally effective concentration of exogenous hrIL-10, failed to attenuate the inhibitory effect of rolipram, PGE2, salbutamol, and 8-Br-cAMP. Anti-IL-10 was similarly inactive when the number of monocytes seeded was increased from 0.5 to 4 x 10(6)/mL or when measurements were made at 42 h post-LPS, a time when the concentration of IL-10 released was maximal. Collectively, these data suggest that in contrast to murine hepatocytes and macrophages, IL-10 does not mediate the inhibitory effect of cAMP-elevating drugs on TNF-alpha generation
AU  - Seldon,PM
AU  - Barnes,PJ
AU  - Giembycz,MA
DO  - 10.1007/BF02737835
EP  - 201
PY  - 1998///
SN  - 1085-9195
SP  - 179
TI  - Interleukin-10 does not mediate the inhibitory effect of PDE-4 inhibitors and other cAMP-elevating drugs on lipopolysaccharide-induced tumors necrosis factor-alpha generation from human peripheral blood monocytes.
T2  - Cell Biochem Biophys
UR  - http://dx.doi.org/10.1007/BF02737835
UR  - https://www.ncbi.nlm.nih.gov/pubmed/9631245
VL  - 29
ER  -
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