Article

Combined effects of IL-12 and IL-18 on the induction of collagen-induced arthritis.

Department of Immunology and Centre for Rheumatic Diseases, University of Glasgow, United Kingdom.
The Journal of Immunology (impact factor: 5.79). 07/2000; 164(12):6495-502. pp.6495-502
Source: PubMed

ABSTRACT IL-18 expression has recently been detected in rheumatoid arthritis (RA) synovial membrane. We investigated the mechanisms by which IL-18-induced collagen-induced arthritis in DBA/1 mice primed intradermally with type II bovine collagen in IFA and boosted i.p. 21 days later with CII in saline. Mice were injected i.p. with rIL-12, rIL-18, or both (100 ng) during days -1 to 4 and again on days 20-24. Control mice received PBS. Mice treated with IL-12 or IL-18 alone developed significantly higher incidence and more severe disease compared with controls. These were elevated further by combination treatment with IL-12 and IL-18. The cytokine treatments led to markedly enhanced synovial hyperplasia, cellular infiltration, and cartilage erosion compared with controls. Cytokine-treated mice produced significantly more IFN-gamma, TNF-alpha, and IL-6 than the controls. Interestingly, IL-18-treated mice produced more TNF-alpha and IL-6, but less IFN-gamma, compared with mice treated with IL-12. Furthermore, splenic macrophages from DBA/1 mice cultured in vitro with IL-18, but not IL-12, produced substantial amounts of TNF-alpha. Mice treated with IL-18 or IL-18 plus IL-12 produced markedly more IgG1 and IgG2a anti-collagen Ab compared with controls, whereas IL-12 treatment only led to an enhanced IgG2a response. Together these results demonstrate that IL-18 can promote collagen-induced inflammatory arthritis through mechanisms that may be distinct from those induced by IL-12.

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Keywords

cartilage erosion
 
collagen-induced inflammatory arthritis
 
combination treatment
 
Control mice
 
Cytokine-treated mice
 
DBA/1 mice
 
DBA/1 mice cultured
 
enhanced IgG2a response
 
higher incidence
 
IFN-gamma
 
IgG2a anti-collagen Ab
 
IL-18 expression
 
IL-18-induced collagen-induced arthritis
 
IL-18-treated mice
 
markedly more IgG1
 
mice
 
rheumatoid arthritis
 
splenic macrophages
 
synovial hyperplasia
 
type II bovine collagen