Streptococcal cell wall-induced arthritis: requirements for IL-4, IL-10, IFN-gamma, and monocyte chemoattractant protein-1.
Intra-articular injection of streptococcal cell wall Ag followed by i.v. challenge ("reactivation") results in a destructive lymphocyte-dependent monoarticular arthritis. To further define the role of immune mechanisms in the model, Abs to Th1 and Th2-related cytokines were evaluated. Treatment of rats with antibodies to IL-4 reduced swelling, while treatment with anti-IL-10 or anti-IFN-gamma either had no effect or slightly enhanced the inflammatory response. These results suggest that Th-2 immune mechanisms may be, at least in part, operative in the model. To more precisely define the role of IL-4, the effects of anti-IL-4 on monocyte chemoattractant protein-1 (MCP-1) expression were evaluated. Initial studies demonstrated that mRNA (as determined by in situ hybridization) and protein (as determined by immunofluorescence) for MCP-1 were detectable in inflamed synovial tissue in a time-dependent manner. Anti-IL-4 treatment significantly reduced the expression of mRNA for MCP-1 24 and 72 h after reactivation. In addition, anti-MCP-1 inhibited swelling and reduced influx of (111)In-labeled T cells. These data suggest that the reactivation model of streptococcal cell wall Ag-induced arthritis is Th-2 dependent, and that an inter-relationship exists between IL-4 and the expression of MCP-1.
Schimmer
R C
RC
Department of Surgery, University of Zurich Medical School, Switzerland.
Schrier
D J
DJ
Flory
C M
CM
Laemont
K D
KD
Tung
D
D
Metz
A L
AL
Friedl
H P
HP
Conroy
M C
MC
Warren
J S
JS
Beck
B
B
Ward
P A
PA
D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D001168:Arthritis / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D002465:Cell Movement / Q000276:immunology; D018932:Chemokine CCL2 / Q000032:analysis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D005260:Female; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007270:Injections, Intra-Articular; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000276:immunology / Q000502:physiology*; D016753:Interleukin-10 / Q000276:immunology / Q000502:physiology*; D015847:Interleukin-4 / Q000276:immunology / Q000502:physiology*; D010457:Peptidoglycan / Q000008:administration & dosage*; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013291:Streptococcus / Q000276:immunology*; D013601:T-Lymphocytes / Q000473:pathology
D019138:Antibodies, Blocking; D018932:Chemokine CCL2; D010457:Peptidoglycan; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma