Insulin-like growth factor I accelerates recovery of articular cartilage proteoglycan synthesis in culture after inhibition by interleukin 1.
Interleukin 1 (IL-1) is a cytokine which induces cartilage proteoglycan (PG) depletion by inhibiting PG synthesis and increasing PG breakdown. Insulin-like growth factor I (IGF-I), in contrast, is known to promote matrix formation. We examined the effects of both mediators in a bovine tissue culture model. IL-1 dose-dependently inhibited PG formation of articular cartilage [half-maximal effect (EC50) at 4 ng/ml], while PG synthesis was increased by IGF-I (EC50 = 15 ng/ml). After inhibition of PG formation with IL-1 for 2 days and subsequent removal of free IL-1, addition of IGF-I dose-dependently accelerated restoration of the original rate of synthesis with a half-maximal effect at 20 ng/ml and a maximal effect at 50 ng/ml. The IGF-I concentration required to elicit a half-maximal effect on cartilage PG synthesis remained constant in the absence or presence of IL-1. We therefore conclude that inhibition of cartilage PG synthesis by IL-1 is not effected by damage to the IGF receptor. Synovial fluid (SF) of 40 patients with rheumatoid arthritis (RA) was found to contain 64 +/- 6 ng IGF-I/ml (mean +/- SEM). The reported effects of IGF-I in vitro therefore occurred at concentrations comparable to those present in joints in vivo. IL-1 beta was detectable (> 0.5 pg/ml) in 38 of 40 RA-SF samples (mean 28 +/- 6 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
Neidel
J
J
Department of Orthopaedics, Center for Rheumatology, Bad Bramstedt, Germany.
Schulze
M
M
Sova
L
L
D001172:Arthritis, Rheumatoid / Q000378:metabolism; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000494:pharmacology / Q000502:physiology*; D007375:Interleukin-1 / Q000032:analysis / Q000494:pharmacology / Q000502:physiology*; D011509:Proteoglycans / Q000096:biosynthesis*; D013582:Synovial Fluid / Q000737:chemistry / Q000378:metabolism
D007375:Interleukin-1; D011509:Proteoglycans; D007334:Insulin-Like Growth Factor I