Recombinant human interleukin-1 beta-induced increase in levels of proteoglycans, stromelysin, and leukocytes in rabbit synovial fluid.
OBJECTIVE
To evaluate the effects of intraarticular injection of recombinant human interleukin-1 beta (IL-1 beta) on levels of proteoglycans, stromelysin, and leukocytes in rabbit synovial fluid (SF), and to determine the effects of leukocyte depletion on SF proteoglycan and stromelysin levels.


METHODS
Levels of leukocytes and of proteoglycans, stromelysin, and collagenase were evaluated 12 hours after the intraarticular injection of various doses of IL-1, and over a 24-hour period after injection at a single dose level. We used a monoclonal antibody (MAb) against leukocyte integrins, which markedly depressed leukocyte accumulation in SF, to evaluate the role of synovial leukocytes on IL-1-induced increases in SF proteoglycan and stromelysin levels.


RESULTS
Levels of both proteoglycans and stromelysin increased in the IL-1-injected joints between 4 hours and 24 hours after the injection of a single 200-ng dose of IL-1. The highest levels of stromelysin and proteoglycans were achieved with IL-1 doses greater than or equal to 100 ng. Infiltration of polymorphonuclear cells (PMN) into the joint fluid of the IL-1-injected rabbits also increased, in a dose-dependent manner. Treatment of rabbits with MAb 1B4 markedly reduced infiltration of PMN into the joint, without affecting either stromelysin or proteoglycan levels.


CONCLUSIONS
Taken together, the data suggest that there is a coordinate increase in SF stromelysin and proteoglycan levels in rabbits injected with IL-1, and that leukocytes play a minimal role in the accumulation of proteoglycans and stromelysin in the SF.
McDonnell
J
J
Merck Research Laboratories, Rahway, New Jersey 07065.
Hoerrner
L A
LA
Lark
M W
MW
Harper
C
C
Dey
T
T
Lobner
J
J
Eiermann
G
G
Kazazis
D
D
Singer
I I
II
Moore
V L
VL
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D007375:Interleukin-1 / Q000494:pharmacology*; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000378:metabolism*; D003012:Microbial Collagenase / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D009504:Neutrophils / Q000502:physiology*; D011509:Proteoglycans / Q000378:metabolism*; D011817:Rabbits; D011994:Recombinant Proteins; D013582:Synovial Fluid / Q000378:metabolism*; D013997:Time Factors
D007375:Interleukin-1; D009363:Neoplasm Proteins; D011509:Proteoglycans; D011994:Recombinant Proteins; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D003012:Microbial Collagenase