Nonsteroidal antiinflammatory drugs: effects on normal and interleukin 1 treated human articular chondrocyte metabolism in vitro.
OBJECTIVE
To test the effects of nonsteroidal antiinflammatory drugs (NSAID), naproxen, ibuprofen and diclofenac, and salicylates on normal and interleukin 1 (IL-1) treated human articular chondrocyte metabolism in vitro.


METHODS
Normal adult human articular chondrocytes were isolated and cultured as primary monolayers; the cells were treated with NSAID and salicylates at low and high plating density for assessing effects on proliferation and matrix synthesis and IL-1 modulated cell metabolism, respectively.


RESULTS
Cell proliferation was inhibited by ibuprofen and high doses of salicylates. Glycosaminoglycan (GAG) synthesis was stimulated by ibuprofen at 10 micrograms/ml but was not changed by any other drugs at similarly low concentrations; at medium to high concentrations, only the salicylates inhibited GAG synthesis. Collagen synthesis was unaffected by any drug at the concentrations tested. IL-1 induced prostaglandin E2 release was completely inhibited by the NSAID and partially inhibited by the salicylates. IL-1 induced IL-6 release was inhibited by ibuprofen and the salicylates where as IL-1 induced APMA-activated collagenase was only inhibited by the salicylates.


CONCLUSIONS
Normal human chondrocytes respond differentially to naproxen, ibuprofen, dicolfenac, and the salicylates; these observations suggest that each drug may exhibit unique attributes with respect to longterm efficacy on cartilage metabolism.
Smith
R L
RL
Orthopaedic Research Laboratory, Stanford University School of Medicine, CA, USA.
Kajiyama
G
G
Lane
N E
NE
D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D017364:Collagenases / Q000378:metabolism; D004008:Diclofenac / Q000494:pharmacology*; D015232:Dinoprostone / Q000037:antagonists & inhibitors; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D009288:Naproxen / Q000494:pharmacology*; D012016:Reference Values; D012459:Salicylates / Q000494:pharmacology
D007375:Interleukin-1; D015850:Interleukin-6; D012459:Salicylates; D004008:Diclofenac; D009288:Naproxen; D017364:Collagenases; D015232:Dinoprostone; D007052:Ibuprofen