In vivo cytokine secretion and NF-kappaB activation around titanium and copper implants.
The early biological response at titanium (Ti), copper (Cu)-coated Ti and sham sites was evaluated in an in vivo rat model. Material surface chemical and topographical properties were characterized using Auger electron spectroscopy, energy dispersive X-ray spectroscopy and interferometry, respectively. The number of leukocytes, cell types and cell viability (release of lactate dehydrogenase) were determined in the implant-interface exudate. The contents of activated nuclear transcription factor NF-kappaB, interleukin-6 (IL-6) and interleukin-10 (IL-10) were determined by enzyme linked immunosorbent assay. An increase in the number of leukocytes, in particular, polymorphonuclear leukocytes, was observed between 12 and 48 h around Cu. A marked decrease of exudate cell viability was found around Cu after 48 h. The total amounts of activated NF-kappaB after 12 h was highest in Ti exudates whereas after 48 h the highest amount of NF-kappaB was detected around Cu. The levels of cytokine IL-6 were consistently high around Cu at both time periods. No differences in IL-10 contents were detected, irrespective of material/sham and time. The results show that materials with different toxicity grades (titanium with low and copper with high toxicity) exhibit early differences in the activation of NF-kappaB, extracellular expression and secretion of mediators, causing major differences in inflammatory cell accumulation and death in vivo.
Department of Biomaterials, Institute of Surgical Sciences, Sahlgrenska Academy at Göteborg University, Medicinaregatan 8B, Box 412, SE-40531 Göteborg, Sweden. felicia.suska@biomaterials.gu.se
Felicia
F
Suska
Christina
C
Gretzer
Marco
M
Esposito
Lena
L
Emanuelsson
Ann
A
Wennerberg
Pentti
P
Tengvall
Peter
P
Thomsen
D000818:Animals; D002470:Cell Survival; D002634:Chemotaxis, Leukocyte; D020099:Coated Materials, Biocompatible; D003300:Copper; D005122:Exudates and Transudates; D005260:Female; D005549:Foreign-Body Reaction / Q000209:etiology* / Q000378:metabolism; D020007:Implants, Experimental; D016753:Interleukin-10 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008422:Materials Testing; D009000:Monocytes / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014025:Titanium
D020099:Coated Materials, Biocompatible; D015850:Interleukin-6; D016328:NF-kappa B; D016753:Interleukin-10; D003300:Copper; D014025:Titanium