Production and distribution of interleukin 15 and its receptors (IL-15R alpha and IL-R2 beta) in the implant interface tissues obtained during revision of failed total joint replacement

Failure of total joint replacement (TJR) is a major problem and it is estim ated that 15-20% of TJR will fail within 5-10 years after implantation. Mos t TJR is attributed to aseptic loosening of the implants in association wit h resorption of related bone due to the release of bone-associated cytokine s. IL-15 is a cytokine that activates T cells and natural killer (NK) cells . IL-15 protein is ubiquitous and is expressed in many tissues and cell typ es. Using immunohistochemical techniques, we demonstrated the expression of IL-15 and its receptors IL-15R alpha and IL-2R beta in the interface tissu es obtained from revision surgery. Both IL-15 protein and IL-15R alpha were observed in macrophages, multinucleated giant cells and endothelial cells around blood vessels. Both the SDS-PAGE and western blot revealed multiple bands and after stages of glycosylation, this resulted in a band at 13 KDa which corresponds to the IL-15 protein. Again RT-PCR results demonstrated a band of 420 bp corresponding to the IL-15 protein. In addition, using U937 cells, the expression of both IL-15 protein and IL-15R alpha. were conside rably up-regulated when challenged with retrieved metal particles. Our resu lts illustrated the IL-15 to be an intact protein and that it is stored in the cytoplasm. A dye exclusion cell viability test displayed an increase in toxicity with an increase in the amount of metal particles added. There wa s a discrepancy between abundant IL-15 mRNA, intracellularly detectable IL- 15 protein and apparently inefficient secretion. This suggests that IL-15 p rotein production is predominantly regulated post-transcriptionally and thi s is indicated by its strict regulation, especially at cell trafficking. Fi nally, unlike IL-2, IL-15 plays a certain role in bone resorption that lead s to failed joint prostheses. It is apparent that this cytokine is an impor tant T cell mediated immune response which needs further research.