Modulation of synovial cell function by somatostatin in patients with rheumatoid arthritis

Abstract

Objective. To elucidate the role of neurologic, endocrine, and immune system interactions in the development of pathologic responses in patients with rheumatoid arthritis (RA), we studied somatostatin (SOM) production and somatostatin receptor (SOMR) expression in RA synovium and its function in patients with RA.Methods. The effects of SOM on proinflammatory cytokine (interleukin-6 [IL-6] and IL-8) and collagenase production by RA synovial cells were estimated by enzyme-linked immunosorbent assay, and their messenger RNA expression was assessed by reverse transcription-polymerase chain reaction (RT-PCR) using limiting dilutions of the complementary DNA. The expression of SOMR by RA synovial cells was also studied by RT-PCR. Local production of SOM was estimated by RT-PCR and immunohistochemical staining. Results. Physiologic concentrations (-lO-''W ofSOM inhibited proliferation of RA synovial cells. The production of proinflammatory cytokines and matrix metalloproteinases by RA synovial cells was also modulated by SOM. SOMR subtypes 1 and 2 were expressed on fibroblast-like synovial cells, and the expression of SOMR-2 was up-regulated by proinflammatory cytokine treatment of the synovial cells from patients with RA. RA fibroblast-like cells synthesized SOM by themselves, suggesting that SOM acts as an autocrine regulator of synovial cell function in patients with RA.

The role of cortistatin in the human immune system

“…In our studies we did not observe a reduction in the severity of rat adjuvant arthritis using the SRIF analogue octreotide (ten Bokum et al, 1999b). Takeba et al has shown that SRIF at physiological concentrations inhibits the in vitro proliferation of fibroblast-like synovial cells from RA patients (Takeba et al, 1997). Cultured fibroblast-like synovial cells express mRNA for both sst 1 and sst 2 , while sst 2 mRNA is sensitive to upregulation by proinflammatory stimuli.…”

“…In biopsies of rheumatoid synovium sst 2 expression has been detected on macrophages, as well as on endothelial cells of venules (especially high endothelial venules) (Takeba et al, 1997;ten Bokum et al, 1999a;Vanhagen et al, 1994a). SRIF can be produced by synovial cells or secreted by sensory nerve endings into the joint capsule (Takeba et al, 1997). These data point towards the existence of a SRIF immunoregulatory circuit within the rheumatoid synovium.…”

Somatostatin receptor subtypes in human immune cells

“…Besides the earlier mentioned correlation between inflammation and uptake of radiolabelled octreotide in scintigraphy (19), it was also demonstrated that somatostatin inhibits both proliferation of synovial cells from patients with rheumatoid arthritis and production of the pro-inflammatory cytokines IL-6 and IL-8 (40). Notably, these authors also report the presence of sst 1 and sst 2 on fibroblast-like synovial cells and the absence of receptors on T-lymphocytes.…”

Differential antiinflammatory and antinociceptive effects of the somatostatin analogs octreotide and pasireotide in a mouse model of immune‐mediated arthritis

“…In RA patients, somatostatin receptors have been detected in the synovial tissue of affected joints (39,40). Activation of these receptors using SRIF-14 inhibited the proliferation of synovial cells from RA patients in vitro (41). However, our knowledge about the somatostatin receptor subtypes involved in the antiinflammatory and antinociceptive actions of SRIF-14 is limited.…”