Effects of a PEGylated soluble TNF receptor type 1 (PEG sTNF-RI) on cytokine expression in adjuvant arthritis.
OBJECTIVE
To investigate the effects of TNF blocking therapy on synovial immune activity in rat adjuvant arthritis (AA) by measuring mRNA expression of key macrophage and T cell cytokines during PEG sTNF-RI treatment (10mg/kg) on days 8, 10 and 12.


METHODS
Paw volume was assessed every 3-4 days. Ankles were removed for quantitative radiology and histology and synovial membrane removed to determine cytokine mRNA expression using semi-quantitative RT-PCR. T cells in joints were quantified by immunohistochemistry.


RESULTS
Paw volume was significantly decreased in rats treated with PEG STNF-RI from days 12 to 17. Histology scores and synovial T cell numbers were reduced on days 13 and 17 and radiology scores significantly reduced on day 13. Expression of synovial TNF, IFN-gamma, IL-17, IL-2 and IL-4 mRNA was unchanged in treated rats and TGF-beta expression was significantly increased at day 13.


CONCLUSIONS
PEG sTNF-RI attenuates AA and disease recurs after treatment ceases, similar to human rheumatoid arthritis. Continued TNF production and/or ongoing T cell activity, may explain the recrudescence of disease once treatment is stopped.
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000235:genetics*; D000068800:Etanercept; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D007074:Immunoglobulin G / Q000494:pharmacology*; D008198:Lymph Nodes / Q000502:physiology; D008297:Male; D011092:Polyethylene Glycols / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*; D047888:Receptors, Tumor Necrosis Factor, Type I; D013583:Synovial Membrane / Q000276:immunology; D053319:Tumor Necrosis Factor Decoy Receptors
D016207:Cytokines; D007074:Immunoglobulin G; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D053319:Tumor Necrosis Factor Decoy Receptors; C069521:recombinant human tumor necrosis factor-binding protein-1; D011092:Polyethylene Glycols; D000068800:Etanercept