In vitro effects of non-steroidal anti-inflammatory drugs on cytokine, prostanoid and matrix metalloproteinase production by interface membranes from loose hip or knee endoprostheses.
OBJECTIVE
To study the effects of the non-steroidal anti-inflammatory drugs (NSAIDs) aceclofenac, piroxicam, tenoxicam and indomethacin on cytokine, matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) and prostaglandin E2 (PGE2) production, by interface membranes (IFT), obtained at revision surgery for aseptic loosening of total joint arthroplasty. Involvement of these soluble factors is well documented and probably, a pharmaceutically induced inhibition of them might retard loosening.


METHODS
IFTs from 10 patients with a loose hip or knee endoprosthesis were collected. The possibility of septic loosening was thoroughly excluded by histopathologic and microbiologic evaluation. IFTs were cultured in the absence or presence of the tested drugs and the levels of the soluble mediators were determined, using electrophoretic and enzyme-linked immunosorbent assay techniques. Paracetamol was used as neutral drug.


RESULTS
All NSAIDs exhibited a pronounced inhibitory effect upon the production of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha). This specific effect on IL-6 is reported in the literature for the first time. The majority of NSAIDs also induced the production of IL-1beta in an adequate portion of samples. These drugs did not have a clear effect on MMP synthesis, but they had a stimulatory tendency on TIMP-1 production. Paracetamol, significantly decreased the synthesis of TNF-alpha and that of the gelatinases.


CONCLUSIONS
Our in vitro results are encouraging, since it appears that the action of NSAIDs, globally considered, may be beneficial upon the loosening process. The inhibitory effect of paracetamol upon TNF-alpha and gelatinases is intriguing. Our data, if supported by similar observations, probably justify performance of long-term clinical trials.
Syggelos
S A
SA
Department of Orthopaedics, School of Medicine, University of Patras, Rio, Patras, Greece.
Giannopoulou
E
E
Gouvousis
P A
PA
Andonopoulos
A P
AP
Aletras
A J
AJ
Panagiotopoulos
E
E
D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects; D016207:Cytokines / Q000187:drug effects* / Q000378:metabolism; D004008:Diclofenac / Q000031:analogs & derivatives / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D006622:Hip Prosthesis / Q000009:adverse effects; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007720:Knee Prosthesis / Q000009:adverse effects; D020782:Matrix Metalloproteinases / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D010894:Piroxicam / Q000031:analogs & derivatives / Q000494:pharmacology; D019714:Tissue Inhibitor of Metalloproteinases / Q000187:drug effects* / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D019714:Tissue Inhibitor of Metalloproteinases; D010894:Piroxicam; D004008:Diclofenac; D020782:Matrix Metalloproteinases; D015232:Dinoprostone; C056498:aceclofenac; D007213:Indomethacin; C032801:tenoxicam