Raap, T. and Justen, H. P. and Miller, L. E. and Cutolo, M. and Schoelmerich, Juergen and Straub, Rainer H. (2000) Neurotransmitter modulation of interleukin 6 (IL-6) and IL-8 secretion of synovial fibroblasts in patients with rheumatoid arthritis compared to osteoarthritis. JOURNAL OF RHEUMATOLOGY, 27 (11). pp. 2558-2565. ISSN 0315-162X
Full text not available from this repository. (Request a copy)Abstract
Objective. The sensory nervous system with the 2 neurotransmitters substance P (SP) and calcitonin gene related peptide (CGRP) is proinflammatory in experimental models of arthritis. The role of the sympathetic nervous system with norepinephrine (NE), adenosine, beta -endorphin, and methionine enkephalin (MENK) is not clearly understood. We studied the influence of these neurotransmitters; on secretion of interleukin 6 (IL-6) and IL-8 in primary cultures of synovial fibroblasts of patients with rheumatoid arthritis (RA) compared to osteoarthritis (OA). Methods. Fibroblasts were isolated using fresh synovial tissue of 5 patients with RA and 5 with OA who underwent knee joint replacement surgery. Modulation of spontaneous secretion of IL-6 and IL-8 was investigated in vitro using the neurotransmitters noted above. Results. In RA fibroblasts, CGRP increased IL-6 and IL-8 secretion at 10(-10) to 10(-8) M (p at least < 0.01), which was not observed in OA fibroblasts. SP had no effect on either cytokine in RA fibroblasts but stimulated IL-8 secretion at 10(-8) M in OA fibroblasts (p < 0.01). In RA fibroblasts, adenosine and NE inhibited secretion of both cytokines at low concentrations (10(-8) M: p < 0.01). However, in OA fibroblasts there was a NE induced increase of IL-8 and IL-6 secretion at 10(-7) and 10(-6) M (p < 0.01), but no inhibition at lower concentrations (10(-8) M: p = NS). In RA fibroblasts. beta -endorphin and MENK inhibited IL-8 secretion at 10(-9) to 10(-7) M (p < 0.01), whereas in OA fibroblasts the dose response curve was shifted to lower concentrations (10(-12) M, 10(-11) M; p < 0.01). Conclusion. In OA fibroblasts, the sympathetic neurotransmitters were stimulatory at higher concentrations. CGRP was the most potent stimulatory neurotransmitter in RA fibroblasts: whereas the sympathetic adenosine, NE, beta -endorphin. and MENK were inhibitory. This indicates a dualism of action of sympathetic and sensory neurotransmitters, with inhibitory and stimulatory effects on cytokine secretion of RA fibroblasts.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENE-RELATED PEPTIDE; TUMOR-NECROSIS-FACTOR; SUBSTANCE-P; HUMAN-MONOCYTES; OPIOID PEPTIDE; FACTOR-ALPHA; RECEPTOR; INFLAMMATION; STIMULATION; EXPRESSION; rheumatoid arthritis; osteoarthritis; neurotransmitter; fibroblast; interleukin 6; interleukin 8 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 21 Mar 2022 07:18 |
| Last Modified: | 21 Mar 2022 07:18 |
| URI: | https://pred.uni-regensburg.de/id/eprint/42103 |
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