Abstract
It is well known that cytokines are highly involved in the disease process of rheumatoid arthritis (RA). Recently, targeting of neuropeptides has been suggested to have potential therapeutic effects in RA. The aim of this study was to investigate possible interrelations between five neuropeptides (bombesin/gastrin-releasing peptide (BN/GRP), substance P (SP), vasoactive intestinal peptide, calcitonin-gene-related peptide, and neuropeptide Y) and the three cytokines tumour necrosis factor (TNF)-α, IL-6, and monocyte chemoattractant protein-1 in synovial fluid of patients with RA. We also investigated possible interrelations between these neuropeptides and soluble TNF receptor 1 in serum from RA patients. Synovial fluid and sera were collected and assayed with ELISA or RIA. The most interesting findings were correlations between BN/GRP and SP and the cytokines. Thus, in synovial fluid, the concentrations of BN/GRP and SP grouped together with IL-6, and SP also grouped together with TNF-α and monocyte chemoattractant protein-1. BN/GRP and SP concentrations in synovial fluid also grouped together with the erythrocyte sedimentation rate. In the sera, BN/GRP concentrations and soluble TNF receptor 1 concentrations were correlated. These results are of interest because blocking of SP effects has long been discussed in relation to RA treatment and because BN/GRP is known to have trophic and growth-promoting effects and to play a role in inflammation and wound healing. Furthermore, the observations strengthen a suggestion that combination treatment with agents interfering with neuropeptides and cytokines would be efficacious in the treatment of RA. In conclusion, BN/GRP and SP are involved together with cytokines in the neuroimmunomodulation that occurs in the arthritic joint.
Highlights
It has long been known that neuropeptides are secreted locally during immune responses [1], and that they are involved in vasodilation and plasma extravasation, that is, neurogenic inflammation [2,3]
We studied the concentrations of sTNFR1 in relation to these neuropeptides in serum
The concentrations of immunoreactive IL-6 in synovial fluid were detected in 95% of the patients with rheumatoid arthritis (RA)
Summary
It has long been known that neuropeptides are secreted locally during immune responses [1], and that they are involved in vasodilation and plasma extravasation, that is, neurogenic inflammation [2,3]. SP has known proinflammatory properties, enhancing the proliferation of rheumatoid synoviocytes [6] and inducing the release of the proinflammatory mediator prostaglandin E2 and destructive enzymes such as collagenase [6]. An increased level of SP has been observed in the synovial fluid from RA patients [7,8,9,10,11]. Another neuropeptide is gastrin-releasing peptide (GRP) [12], the mammalian homologue of bombesin (BN), a tetradecapeptide originally isolated from the skin of the frog Bombina bombina [13].
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