IL-18 Neutralization Modifies Disease Activity in Model of Rheumatoid Arthritis

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IL-18 Neutralization Modifies Disease Activity in Model of Rheumatoid Arthritis

NEW YORK (Reuters Health) Jan 08 - Using antibody or a binding protein to

neutralize interleukin-18 (IL-18) reduces signs of inflammation and cartilage

degradation in a murine model of rheumatoid arthritis, a multinational team of

investigators reports.

IL-18 appears to modulate synovial inflammation in rheumatoid arthritis, Dr.

Yolande Chvatchko, of Serono Pharmaceutical Research Institute in Geneva, and

associates point out in the Journal of Clinical Investigation for December. In

their study, they induced an erosive, inflammatory arthritis in mice by

immunizing them with type II collagen.

After clinical signs of disease appeared, the researchers treated one group of

mice with neutralizing rabbit polyclonal anti-mouse anti-IL-18 immunoglobulin G

or placebo. A second group was treated with recombinant human IL-18 binding

protein (rhIL-18BP) or placebo.

Circulating levels of IL-18 were significantly elevated on days 4 and 8 after

the onset of arthritic symptoms. Swelling in both treatment groups was

significantly diminished compared with placebo-treated mice. While the control

mice exhibited synovial inflammation, along with cartilage and subchondral bone

erosions, the severity of these manifestations was reduced in both groups of

treated animals.

The antibody treatment, but not binding protein treatment, decreased cellular

infiltration and synovial hyperplasia. Both treatments reduced serum levels of

cartilage oligomeric matrix protein, a validated marker of cartilage turnover,

and levels of IL-16.

The supernatants from cultured peritoneal macrophages were used to assay

cytokine levels. The binding protein caused levels of tumor necrosis

factor-alpha, interferon-gamma, and IL-6 to be reduced to basal levels.

According to the authors, these results provide " a potential explanation for the

protective effect observed in vivo. "

In addition, they write, " The disease-modifying activity of IL-18 neutralization

in an experimental model of rheumatoid arthritis provides a rationale to test

such a strategy in the clinic. "

J Clin Invest 2001;108:1825-1832.