Dexamethasone attenuation of cytokine-mediated articular cartilage degradation in experimental lapine Haemophilus arthritis.
The role of cytokines in the regulation of articular inflammation and cartilage degradation was evaluated in the rabbit model of Haemophilus influenzae type b arthritis. At 6 and 12 h after intraarticular infection, treatment with IB4 monoclonal antibody to the CD18 leukocyte receptor alone or in combination with dexamethasone resulted in significant reduction of synovial fluid (SF) neutrophil concentration. Treatment with dexamethasone alone was associated with lower SF concentrations of interleukin-1 (IL-1), tumor necrosis factor-alpha, and stromelysin than in other groups. At 24 h after infection, increased cartilage degradation was detected in untreated controls and in animals treated with IB4 alone or in combination with dexamethasone compared with those treated with dexamethasone alone. Multiple regression analyses indicated SF concentration of IL-1 and stromelysin as the significant predictors of cartilage degradation. These data suggest that IL-1 mediates cartilage degradation by regulation of metalloproteinases, such as stromelysin, during acute experimental bacterial arthritis.
Jafari
H S
HS
Dept. of Pediatrics, University of Texas Southwestern Medical Center at Dallas 75235-9063.
Sáez-Llorens
X
X
Paris
M
M
Rinderknecht
S
S
Friedland
I
I
Ehrett
S
S
Severien
C
C
Olsen
K D
KD
Burns
D K
DK
Harper
C F
CF
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015703:Antigens, CD / Q000276:immunology; D001170:Arthritis, Infectious / Q000188:drug therapy*; D018821:CD18 Antigens; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D002443:Ceftriaxone / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D003907:Dexamethasone / Q000627:therapeutic use*; D006192:Haemophilus Infections / Q000188:drug therapy*; D006193:Haemophilus influenzae; D007249:Inflammation / Q000473:pathology; D007270:Injections, Intra-Articular; D007375:Interleukin-1 / Q000032:analysis; D008297:Male; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000032:analysis; D009504:Neutrophils / Q000166:cytology; D011509:Proteoglycans / Q000378:metabolism; D011817:Rabbits; D012044:Regression Analysis; D013582:Synovial Fluid / Q000737:chemistry / Q000166:cytology / Q000382:microbiology; D013583:Synovial Membrane / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D016207:Cytokines; D007375:Interleukin-1; D011509:Proteoglycans; D014409:Tumor Necrosis Factor-alpha; D002443:Ceftriaxone; D003907:Dexamethasone; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3