Regulation of interleukin-18 binding protein production by blood and synovial cells from patients with rheumatoid arthritis.

Abstract

OBJECTIVE:

To study the regulation of interleukin-18 binding protein (IL-18BP) production by rheumatoid arthritis (RA) or control peripheral blood mononuclear cells (PBMCs) and by RA synovial tissue cells, and to compare the levels of IL-18BP messenger RNA (mRNA) expression in whole blood from RA patients and controls.

METHODS:

Unstimulated or phytohemagglutinin and phorbol myristate acetate (PHA/PMA)-stimulated PBMCs from 10 RA patients and 12 healthy controls and unstimulated or PHA/PMA-stimulated synovial tissue cells from 8 RA patients were cultured with or without IL-12 (1 ng/ml) and IL-18 (5 ng/ml) alone or in combination. IL-18BP and interferon-gamma (IFN gamma) levels in supernatants were measured by enzyme-linked immunosorbent assay. Levels of IL-18BP and IFN gamma mRNA expression in whole blood samples from 22 RA patients and 12 healthy controls were determined by quantitative reverse transcriptase-polymerase chain reaction.

RESULTS:

IL-12 decreased the basal levels of IL-18BP production by freshly isolated RA or control PBMCs, but increased those of synovial cells or PHA/PMA-stimulated PBMCs. IL-18 alone had no direct effect on IL-18BP production by PBMCs or RA synovial cells, with or without stimulation. Unstimulated whole blood samples from RA patients showed lower levels of IL-18BP mRNA expression than those from healthy controls.

CONCLUSION:

The production of IL-18BP in response to IL-12 and IL-18 was regulated differently in blood and synovial cells. The difference appears to be related to the level of cell activation.

• Authors: Masanori Kawashima, Daniela Novick, Menachem Rubinstein, Pierre Miossec
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 50 Issue 6 Pg. 1800-5 (Jun 2004) ISSN: 0004-3591 [Print] United States
• PMID: 15188356 (Publication Type: Journal Article)

Chemical References

• Adjuvants, Immunologic
• Glycoproteins
• Intercellular Signaling Peptides and Proteins
• Interleukin-18
• RNA, Messenger
• interleukin-18 binding protein
• Interleukin-12

Topics

• Adjuvants, Immunologic (pharmacology)
• Adult
• Arthritis, Rheumatoid (blood, pathology, physiopathology)
• Cells, Cultured
• Female
• Gene Expression
• Glycoproteins (blood, genetics)
• Humans
• Intercellular Signaling Peptides and Proteins
• Interleukin-12 (pharmacology)
• Interleukin-18 (pharmacology)
• Leukocytes, Mononuclear (cytology, physiology)
• Male
• Middle Aged
• RNA, Messenger (analysis, blood)
• Synovial Membrane (cytology, physiology)
• Up-Regulation (drug effects)