Regulation of IL-18BP production by blood and synovial cells from patients with RA

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Arthritis Rheum. 2004 Jun;50(6):1800-5.

Regulation of interleukin-18 binding protein production by blood and

synovial cells from patients with rheumatoid arthritis.

Kawashima M, Novick D, Rubinstein M, Miossec P.

Unite Mixte Hospices Civils de Lyon-BioMerieux, and Hospital Edouard

Herriot, Lyon, France.

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.

PMID: 15188356

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