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


CONCLUSIONS
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.
Kawashima
Masanori
M
Unité Mixte Hospices Civils de Lyon-BioMérieux, and Hospital Edouard Herriot, Lyon, France.
Novick
Daniela
D
Rubinstein
Menachem
M
Miossec
Pierre
P
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D006023:Glycoproteins / Q000097:blood / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D018664:Interleukin-12 / Q000494:pharmacology; D020382:Interleukin-18 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis / Q000097:blood; D013583:Synovial Membrane / Q000166:cytology / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects
D000276:Adjuvants, Immunologic; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18; D012333:RNA, Messenger; C118370:interleukin-18 binding protein; D018664:Interleukin-12