The roles of interleukin-18 in collagen-induced arthritis in the BB rat

X. J. Ye, B. Tang, Z. Ma, Andrew Kang, Linda Myers, M. A. Cremer

Research output: Contribution to journalArticle

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Abstract

Interleukin (IL)-18 is a member of the IL-1 cytokine family. Its expression is increased in rheumatoid arthritis synovium, and its proinflammatory effects have been demonstrated in experimental models of murine arthritis. Here, we investigate the actions of varying doses of recombinant rat IL-18 (rIL-18) on the course of type II collagen-induced arthritis (CIA) in BB rats, including clinical and immune events, plus splenic cytokine production. Small doses of rIL-18 (10 and 50 μg/rat) administered intraperitoneally (i.p.) increased arthritis incidence and severity (P < 0.01) when a low-potency CII preparation was used for immunization. IgG1 and IgG2a anti-CII antibody levels were significantly greater in rats given 10 and 50 μg rIL-18 doses than controls. rIL-18 significantly increased levels of proinflammatory cytokines [interferon (IFN)-γ, IL-2, tumour necrosis factor (TNF)-α and IL-6] produced by splenocyte cultures. Larger doses of rIL-18 (300 μg/rat) suppressed arthritis and immunity. To ascertain whether the pro-arthritic effects of IL-18 could be attenuated, rats were treated with neutralizing rabbit anti-rIL-18 IgG before immunization with a high-potency CII preparation. When given serially for 3 weeks, the incidence and severity of CIA, in addition to anti-CII IgG2a and splenic IL-6 and IFN-γ production, were all significantly reduced. Similar results were noted when antibody was given twice, just before arthritis onset. These results demonstrate that IL-18 plays an important proinflammatory role in the pathogenesis of CIA which is achieved, in part, by an immunostimulatory action. Neutralizing endogenous IL-18 with antibodies attenuated CIA, CII immunity and cytokine responses. These studies support the use of IL-18 antagonists as treatments for inflammatory arthritis.

Original languageEnglish (US)
Pages (from-to)440-447
Number of pages8
JournalClinical and Experimental Immunology
Volume136
Issue number3
DOIs
StatePublished - Jun 1 2004

Fingerprint

Inbred BB Rats
Interleukin-18
Experimental Arthritis
Arthritis
Cytokines
Interferons
Immunity
Immunization
Interleukin-6
Immunoglobulin G
Synovial Membrane
Antibodies
Incidence
Interleukin-1
Interleukin-10
Interleukin-2
Anti-Idiotypic Antibodies
Rheumatoid Arthritis
Theoretical Models

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

The roles of interleukin-18 in collagen-induced arthritis in the BB rat. / Ye, X. J.; Tang, B.; Ma, Z.; Kang, Andrew; Myers, Linda; Cremer, M. A.

In: Clinical and Experimental Immunology, Vol. 136, No. 3, 01.06.2004, p. 440-447.

Research output: Contribution to journalArticle

Ye, X. J. ; Tang, B. ; Ma, Z. ; Kang, Andrew ; Myers, Linda ; Cremer, M. A. / The roles of interleukin-18 in collagen-induced arthritis in the BB rat. In: Clinical and Experimental Immunology. 2004 ; Vol. 136, No. 3. pp. 440-447.
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