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Arthritis Res. 2001; 3(Suppl A): P019.
Published online Jan 26, 2001. doi:  10.1186/ar188
PMCID: PMC3273185
Substance P and its cleavage products: effects on interleukin-1 secretion of rheumatoid arthritis monocytes/macrophages
E Wagner,1 G Partsch,2 and A Dunky1
15th Medical Department, Wilhelminenspital, Vienna, Austria
2Ludwig Boltzmann Institute of Rheumatology and Balneology, Vienna, Oberlaa, Austria
Supplement
21st European Workshop for Rheumatology Research
Conference
21st European Workshop for Rheumatology Research
1-4 March 2001
Vienna, Austria
Received January 15, 2001
Introduction
Clinical observations in man and experimental studies support the importance of neurogenic mechanisms in the initiation and perpetuation of inflammation. A leading role is attributed to substance P (SP), a tachykinin that besides its role in pain transmission in the central nervous system is also secreted antidromically from peripheral nerve endings into tissue in response to various stimuli. Since SP might be cleaved into several cleavage products (CLP) in the synovial fluid, we determined the effects of SP and its CLPs on the production of IL-1 by monocytes/macrophages (MO) from patients with rheumatoid arthritis.
Methods
MO from venous blood were separated and stimulated with SP and its CLPs in various concentrations without and with LPS stimulation (1 μg/ml). The IL-1 concentration in the supernatant was determined by ELISA. The CLPs SP 1-4, SP 4-11, SP 6-11, SP 7-11 were applied in the experiments.
Results
SP and its CLPs (without LPS) had only weak and low (in pM range) effects on IL-1 secretion. The stimulating effect of SP and SP 7-11 was pronounced at lower concentrations, at higher concentrations inhibition was observed. The other CLPs did not show significant effects.
The same result was observed in MO with prior LPS stimulation. However, with LPS there was an increase of IL-1 in the nMolar range.
Discussion
In contrast to the findings of other authors SP and SP 7-11 at higher concentrations inhibited IL-1 release from MO . The effects were similar in LPS stimulated and LPS unstimulated MO, therfore not due to full LPS stimulation at the concentration of 1 μg/ml. This could point to a mechanism of action different from the classical neurokinin receptor of SP and CLPs on MO regarding cytokine secretion.
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