Melatonin influences interleukin-12 and nitric oxide production by primary cultures of rheumatoid synovial macrophages and THP-1 cells

Maurizio Cutolo, Barbara Villaggio, Federica Candido, Sandra Valenti, Massimo Giusti, Lamberto Felli, Alberto Sulli, Silvano Accardo

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Because some of the clinical symptoms related to rheumatoid arthritis (RA) synovitis, such as joint morning stiffness and gelling, might be related to the effects exerted by the diurnal rhythmicity of the neurohormone melatonin (MLT) on synovial immune cell activation, we decided to evaluate the influence of MLT on the production of IL-12 and nitric oxide (NO) on primary cultures of RA synovial macrophages. Synovial macrophages were also prestimulated with lipopolysaccaride (LPS). Results were compared with those obtained on cultured human myeloid monocytic cells (THP-1). A significant increase in IL-12 (p = 0.01) was found in media of MLT-stimulated synovial macrophages versus RMPI-treated synovial macrophage controls. Interestingly, a significant decrease of IL-12 (p <0.0001) was observed in media of synovial macrophages previously activated with LPS and then treated with MLT, when compared to synovial macrophages treated with LPS alone. A significant increase in NO levels (p = 0.01) was found in MLT-stimulated synovial macrophages versus RMPI-treated synovial macrophage controls. Interestingly, a nonsignificant increase of NO levels was observed in media of synovial macrophages previously activated with LPS and then treated with MLT, when compared to synovial macrophages treated with LPS alone. Finally, a significant increase in IL-12 (p = 0.03) and NO (p = 0.002) concentrations was observed in media of MLT-stimulated THP-1 cells versus RMPI-treated controls. Our results therefore show that MLT induces IL-12 secretion and NO production by unstimulated cultured RA synovial macrophages and human monocytic myeloid THP-1 cells. The unexpected and opposite effects on IL-12 and NO production in RA synovial macrophages treated with LPS may be related to dose-dependent mechanisms exerted by MLT or to altered cell priming in RA macrophages; these are matters of our further research. This study strongly supports the role of MLT in immune response modulation and in particular suggests a close relationship between diurnal rhythmicity of neuroendocrine pathways, cytokine and reactive oxygen intermediate production by monocyte/macrophages, and synovial arthritis symptomatology, at least in RA.

Original languageEnglish
Pages (from-to)246-254
Number of pages9
JournalAnnals of the New York Academy of Sciences
Volume876
DOIs
Publication statusPublished - 1999

Fingerprint

Macrophages
Melatonin
Interleukin-12
Cell culture
Nitric Oxide
Rheumatoid Arthritis
Periodicity
Cells
Synovitis
Myeloid Cells
Arthritis
Neurotransmitter Agents
Monocytes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Melatonin influences interleukin-12 and nitric oxide production by primary cultures of rheumatoid synovial macrophages and THP-1 cells. / Cutolo, Maurizio; Villaggio, Barbara; Candido, Federica; Valenti, Sandra; Giusti, Massimo; Felli, Lamberto; Sulli, Alberto; Accardo, Silvano.

In: Annals of the New York Academy of Sciences, Vol. 876, 1999, p. 246-254.

Research output: Contribution to journalArticle

Cutolo, Maurizio ; Villaggio, Barbara ; Candido, Federica ; Valenti, Sandra ; Giusti, Massimo ; Felli, Lamberto ; Sulli, Alberto ; Accardo, Silvano. / Melatonin influences interleukin-12 and nitric oxide production by primary cultures of rheumatoid synovial macrophages and THP-1 cells. In: Annals of the New York Academy of Sciences. 1999 ; Vol. 876. pp. 246-254.
@article{ed11abda384246baba360e2d5850a93d,
title = "Melatonin influences interleukin-12 and nitric oxide production by primary cultures of rheumatoid synovial macrophages and THP-1 cells",
abstract = "Because some of the clinical symptoms related to rheumatoid arthritis (RA) synovitis, such as joint morning stiffness and gelling, might be related to the effects exerted by the diurnal rhythmicity of the neurohormone melatonin (MLT) on synovial immune cell activation, we decided to evaluate the influence of MLT on the production of IL-12 and nitric oxide (NO) on primary cultures of RA synovial macrophages. Synovial macrophages were also prestimulated with lipopolysaccaride (LPS). Results were compared with those obtained on cultured human myeloid monocytic cells (THP-1). A significant increase in IL-12 (p = 0.01) was found in media of MLT-stimulated synovial macrophages versus RMPI-treated synovial macrophage controls. Interestingly, a significant decrease of IL-12 (p <0.0001) was observed in media of synovial macrophages previously activated with LPS and then treated with MLT, when compared to synovial macrophages treated with LPS alone. A significant increase in NO levels (p = 0.01) was found in MLT-stimulated synovial macrophages versus RMPI-treated synovial macrophage controls. Interestingly, a nonsignificant increase of NO levels was observed in media of synovial macrophages previously activated with LPS and then treated with MLT, when compared to synovial macrophages treated with LPS alone. Finally, a significant increase in IL-12 (p = 0.03) and NO (p = 0.002) concentrations was observed in media of MLT-stimulated THP-1 cells versus RMPI-treated controls. Our results therefore show that MLT induces IL-12 secretion and NO production by unstimulated cultured RA synovial macrophages and human monocytic myeloid THP-1 cells. The unexpected and opposite effects on IL-12 and NO production in RA synovial macrophages treated with LPS may be related to dose-dependent mechanisms exerted by MLT or to altered cell priming in RA macrophages; these are matters of our further research. This study strongly supports the role of MLT in immune response modulation and in particular suggests a close relationship between diurnal rhythmicity of neuroendocrine pathways, cytokine and reactive oxygen intermediate production by monocyte/macrophages, and synovial arthritis symptomatology, at least in RA.",
author = "Maurizio Cutolo and Barbara Villaggio and Federica Candido and Sandra Valenti and Massimo Giusti and Lamberto Felli and Alberto Sulli and Silvano Accardo",
year = "1999",
doi = "10.1111/j.1749-6632.1999.tb07645.x",
language = "English",
volume = "876",
pages = "246--254",
journal = "Annals of the New York Academy of Sciences",
issn = "0077-8923",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Melatonin influences interleukin-12 and nitric oxide production by primary cultures of rheumatoid synovial macrophages and THP-1 cells

AU - Cutolo, Maurizio

AU - Villaggio, Barbara

AU - Candido, Federica

AU - Valenti, Sandra

AU - Giusti, Massimo

AU - Felli, Lamberto

AU - Sulli, Alberto

AU - Accardo, Silvano

PY - 1999

Y1 - 1999

N2 - Because some of the clinical symptoms related to rheumatoid arthritis (RA) synovitis, such as joint morning stiffness and gelling, might be related to the effects exerted by the diurnal rhythmicity of the neurohormone melatonin (MLT) on synovial immune cell activation, we decided to evaluate the influence of MLT on the production of IL-12 and nitric oxide (NO) on primary cultures of RA synovial macrophages. Synovial macrophages were also prestimulated with lipopolysaccaride (LPS). Results were compared with those obtained on cultured human myeloid monocytic cells (THP-1). A significant increase in IL-12 (p = 0.01) was found in media of MLT-stimulated synovial macrophages versus RMPI-treated synovial macrophage controls. Interestingly, a significant decrease of IL-12 (p <0.0001) was observed in media of synovial macrophages previously activated with LPS and then treated with MLT, when compared to synovial macrophages treated with LPS alone. A significant increase in NO levels (p = 0.01) was found in MLT-stimulated synovial macrophages versus RMPI-treated synovial macrophage controls. Interestingly, a nonsignificant increase of NO levels was observed in media of synovial macrophages previously activated with LPS and then treated with MLT, when compared to synovial macrophages treated with LPS alone. Finally, a significant increase in IL-12 (p = 0.03) and NO (p = 0.002) concentrations was observed in media of MLT-stimulated THP-1 cells versus RMPI-treated controls. Our results therefore show that MLT induces IL-12 secretion and NO production by unstimulated cultured RA synovial macrophages and human monocytic myeloid THP-1 cells. The unexpected and opposite effects on IL-12 and NO production in RA synovial macrophages treated with LPS may be related to dose-dependent mechanisms exerted by MLT or to altered cell priming in RA macrophages; these are matters of our further research. This study strongly supports the role of MLT in immune response modulation and in particular suggests a close relationship between diurnal rhythmicity of neuroendocrine pathways, cytokine and reactive oxygen intermediate production by monocyte/macrophages, and synovial arthritis symptomatology, at least in RA.

AB - Because some of the clinical symptoms related to rheumatoid arthritis (RA) synovitis, such as joint morning stiffness and gelling, might be related to the effects exerted by the diurnal rhythmicity of the neurohormone melatonin (MLT) on synovial immune cell activation, we decided to evaluate the influence of MLT on the production of IL-12 and nitric oxide (NO) on primary cultures of RA synovial macrophages. Synovial macrophages were also prestimulated with lipopolysaccaride (LPS). Results were compared with those obtained on cultured human myeloid monocytic cells (THP-1). A significant increase in IL-12 (p = 0.01) was found in media of MLT-stimulated synovial macrophages versus RMPI-treated synovial macrophage controls. Interestingly, a significant decrease of IL-12 (p <0.0001) was observed in media of synovial macrophages previously activated with LPS and then treated with MLT, when compared to synovial macrophages treated with LPS alone. A significant increase in NO levels (p = 0.01) was found in MLT-stimulated synovial macrophages versus RMPI-treated synovial macrophage controls. Interestingly, a nonsignificant increase of NO levels was observed in media of synovial macrophages previously activated with LPS and then treated with MLT, when compared to synovial macrophages treated with LPS alone. Finally, a significant increase in IL-12 (p = 0.03) and NO (p = 0.002) concentrations was observed in media of MLT-stimulated THP-1 cells versus RMPI-treated controls. Our results therefore show that MLT induces IL-12 secretion and NO production by unstimulated cultured RA synovial macrophages and human monocytic myeloid THP-1 cells. The unexpected and opposite effects on IL-12 and NO production in RA synovial macrophages treated with LPS may be related to dose-dependent mechanisms exerted by MLT or to altered cell priming in RA macrophages; these are matters of our further research. This study strongly supports the role of MLT in immune response modulation and in particular suggests a close relationship between diurnal rhythmicity of neuroendocrine pathways, cytokine and reactive oxygen intermediate production by monocyte/macrophages, and synovial arthritis symptomatology, at least in RA.

UR - http://www.scopus.com/inward/record.url?scp=0032781606&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032781606&partnerID=8YFLogxK

U2 - 10.1111/j.1749-6632.1999.tb07645.x

DO - 10.1111/j.1749-6632.1999.tb07645.x

M3 - Article

C2 - 10415616

AN - SCOPUS:0032781606

VL - 876

SP - 246

EP - 254

JO - Annals of the New York Academy of Sciences

JF - Annals of the New York Academy of Sciences

SN - 0077-8923

ER -