In vivo protection against interleukin-1-induced articular cartilage damage by transforming growth factor-beta 1: age-related differences.
OBJECTIVE
Transforming growth factor-beta (TGF-beta) has been shown to antagonise interleukin-1 (IL-1) effects in different systems. Investigations were carried out to study whether TGF-beta 1 modulates IL-1 induced inflammation and IL-1 effects on articular cartilage in the murine knee joint.


METHODS
IL-1, TGF-beta 1 or both factors together were injected into the knee joint. Inflammation was studied in whole knee histological sections. Patellar cartilage proteoglycan synthesis was measured using 35S-sulphate incorporation while patellar cartilage glycosaminoglycan content was determined with automated image analysis on joint sections.


RESULTS
Co-injection of TGF-beta 1 and IL-1 resulted in synergistic attraction of inflammatory cells. In contrast, TGF-beta 1 counteracted IL-1 induced suppression of articular cartilage proteoglycan synthesis. Proteoglycan depletion was similar shortly after the last injection of IL-1 or IL-1/TGF-beta 1, but accelerated recovery was found with the combination at later days. This protective effect of TGF-beta 1 could not be demonstrated in older mice.


CONCLUSIONS
TGF-beta 1 aggravates IL-1 induced knee joint inflammation, but counteracts the deleterious effects of IL-1 on articular cartilage proteoglycan synthesis and content. The data indicate that TGF-beta 1 could play an important part in articular cartilage restoration after IL-1 induced proteoglycan depletion.
Department of Rheumatology, University Hospital, Nijmegen, The Netherlands.
H M
HM
van Beuningen
P M
PM
van der Kraan
O J
OJ
Arntz
W B
WB
van den Berg
D000367:Age Factors; D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism*; D004357:Drug Synergism; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010329:Patella / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013585:Synovitis / Q000209:etiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D007375:Interleukin-1; D011509:Proteoglycans; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta