C-reactive protein as an index of disease activity. Comparison of tenidap, cyclophosphamide and dexamethasone in rat adjuvant arthritis.
C-reactive protein (CRP) concentrations are a useful plasma protein measure that correlate with disease severity and radiographic progression in rheumatoid arthritis (RA). We compared 3 drugs with different mechanisms, i.e., tenidap, dexamethasone and cyclophosphamide, on both CRP levels and soft tissue swelling in the rat adjuvant arthritis model. CRP rose from a normal concentration of approximately 400 micrograms/ml during the first phase of adjuvant arthritis to approximately 1200 micrograms/ml (primary response), then fell to approximately 900 micrograms/ml and rose again as the disease became systemic during the secondary response to approximately 1400 micrograms/ml. When treatment was administered prophylactically, tenidap and dexamethasone suppressed both the primary and secondary CRP and swelling responses. Cyclophosphamide was without effect in the primary response, but inhibited both swelling and CRP in the secondary response. When therapeutic treatment was begun after secondary disease was established, only tenidap and dexamethasone inhibited CRP and swelling. Both dexamethasone and cyclophosphamide decreased lymphocyte numbers during treatment whereas lymphocyte numbers were elevated during tenidap treatment, suggesting a different mechanism of action for tenidap. CRP levels were more closely linked to the rate of change of paw swelling (disease progression) than to paw volume.
Otterness
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Pfizer Central Research Division, Department of Immunology and Infectious Diseases, Groton, CT 06340.
Pazoles
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PP
Moore
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Pepys
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MB
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000097:blood / Q000188:drug therapy* / Q000517:prevention & control; D002097:C-Reactive Protein / Q000032:analysis*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D003907:Dexamethasone / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D004487:Edema / Q000517:prevention & control; D005528:Foot; D007211:Indoles / Q000627:therapeutic use*; D007958:Leukocyte Count / Q000187:drug effects; D008214:Lymphocytes / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D000078183:Oxindoles; D051381:Rats
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007211:Indoles; D000078183:Oxindoles; D003907:Dexamethasone; D003520:Cyclophosphamide; D002097:C-Reactive Protein; C062866:tenidap