RGD Reference Report - The roles of interleukin-18 in collagen-induced arthritis in the BB rat. - Rat Genome Database

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

Authors: Ye, XJ  Tang, B  Ma, Z  Kang, AH  Myers, LK  Cremer, MA 
Citation: Ye XJ, etal., Clin Exp Immunol. 2004 Jun;136(3):440-7.
RGD ID: 4889503
Pubmed: PMID:15147345   (View Abstract at PubMed)
PMCID: PMC1809057   (View Article at PubMed Central)
DOI: DOI:10.1111/j.1365-2249.2004.02430.x   (Journal Full-text)

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 microg/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 microg rIL-18 doses than controls. rIL-18 significantly increased levels of proinflammatory cytokines [interferon (IFN)-gamma, IL-2, tumour necrosis factor (TNF)-alpha and IL-6] produced by splenocyte cultures. Larger doses of rIL-18 (300 microg/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-gamma 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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IL18HumanExperimental Arthritis  ISOIl18 (Rattus norvegicus) RGD 
Il18RatExperimental Arthritis  IMP  RGD 
Il18MouseExperimental Arthritis  ISOIl18 (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il18  (interleukin 18)

Genes (Mus musculus)
Il18  (interleukin 18)

Genes (Homo sapiens)
IL18  (interleukin 18)


Additional Information