Adjuvant arthritic (AA) rats exhibit enhanced endotoxin-induced plasma TNF (EIPT) levels.
Adjuvant arthritis (AA) was induced in male Lewis rats by a single FCA (M. butyricum) injection into the tail. At various time periods post FCA injection, AA and control rats were anesthetized and administered E. coli endotoxin (30 mg/kg, i.v.). Plasma samples were obtained at 30, 60, 90, 120 and 150 min following endotoxin administration and assayed for TNF alpha levels by ELISA. Compared to control rats, AA rats exhibited enhanced EIPT levels (706% of control, p < 0.05) which was associated with the onset of inflammatory lesions on days 12-14 post FCA, and remained significantly elevated (> 300% of control, p > 0.05) for at least 30 days post FCA. There were no significant correlations between EIPT levels and hindpaw volumes or body weights. The results of this study support previous observations that AA is associated with macrophage activation and suggest that EIPT levels in AA rats may be a useful parameter for the evaluation of novel antiarthritic agents.
DiMartino
M
M
Dept. of Respiratory/Inflammation Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939.
Slivjak
M
M
Esser
K
K
Wolff
C
C
Smith
E
E
Gagnon
R
R
D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood*; D004731:Endotoxins / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha