Abstract
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/mll, 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-1β was detectable (> 0.5 pg/ml) in 38 of 40 RA-SF samples (mean 28 ± 6 pg/ml). RA synovial tissue in culture released 330 ± 112 pg IL-1β x g tissue−1 x d−1, and this rate could be increased up to 70-fold by the addition of lipopolysaccharides (10 μg/ml). The observed accelerated recovery of cartilage PG synthesis by IGF-I after inhibition by IL-1 may be of relevance in rheumatic diseases like RA since IL-1 levels in RA-SF are known to vary considerably with time, and IGFs have been shown previously to be the most important promotors of cartilage PG synthesis in human SF.
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Neidel, J., Schulze, M. & Sova, L. Insulin-like growth factor I accelerates recovery of articular cartilage proteoglycan synthesis in culture after inhibition by interleukin 1. Arch Orthop Trauma Surg 114, 43–48 (1994). https://doi.org/10.1007/BF00454736
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DOI: https://doi.org/10.1007/BF00454736