Leukocyte-Rich Platelet-Rich Plasma Injections Do Not Up-Modulate Intra-Articular Pro-Inflammatory Cytokines in the Osteoarthritic Knee

Abstract

Introduction: The presence of leukocytes in platelet concentrates is deemed to cause deleterious effects when injected intra articularly. The aim of this study is to analyse both local and systemic effects induced by leukocyte-rich Platelet-rich Plasma (PRP) injections through a proteomic characterization of serial synovial fluid and blood samples obtained from subjects treated for knee OA. Secondary aim was to compare the effects on knee homeostasis and systemic response with those obtained with visco-supplementation.

Methods: Thirty-six OA patients treated either by autologous L-PRP or HA intra-articular knee injections, administered in series of three at one-week intervals, were analyzed. Just before the injection, 1 ml of synovial fluid was collected through the same needle way. In the same time, a peripheral blood sample was obtained and plasma separated. A further peripheral blood sample was collected at 2, 6, and 12 months. L-PRP, plasma and synovial fluid were tested by multiplex bead-based sandwich immunoassay by means of the Bio-Plex suspension array system (Bio-Rad Laboratories) for the presence of pro- and anti-inflammatory cytokines (IL-1beta, IL-6, IL-8, IL-17 and IL-4, IL-10, IL-13) and growth factors (FGF-b, HGF, PDGF-AB/BB).

Results: In general, pro-inflammatory cytokine levels were similar at basal condition and after treatment whereas anti-inflammatory ones were nearly undetectable. L-PRP administration did not modulate significant changes of cytokine concentrations either in synovial fluid or plasma, whatever the time points analyzed. No different trend was observed between L-PRP and HA administration in terms of pro- and anti-inflammatory cytokines, as well as growth factors.

Conclusions: In contrast with the evidence reported by "in vitro" studies, where a cellular pro-inflammatory response appears to be induced by the presence of leukocytes, these results suggest that the presence leukocyte-rich PRP doesn't induce a relevant in vivo up regulation of pro-inflammatory mediators.

Conflict of interest statement

Competing Interests: G. Filardo is consultant and receives institutional support from Fidia Farmaceutici Spa (Italy). He receives Institutional Support from BIOMET (USA) M. Marcacci receives institutional support from: Fidia Farmaceutici Spa (Italy) and BIOMET (USA). E. Kon receives institutional support from Fidia Farmaceutici Spa (Italy), and BIOMET (USA). E. Mariani, L. Cattini, V. Canella, L. Pulsatelli, B. Di Matteo declare no conflict of interest in the authorship or publication of this contribution. The present disclosures do not alter the adherence of all co-authors to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Plasma and synovial fluid concentration of IL-1b and IL-6 in patients treated with L-PRP or HA.

Data are expressed as medians and interquartile ranges; comparisons among time points, as determined by Friedman-ANOVA test, and between L-PRP and HA treatments, as determined by the Mann-Whitney U test, are not significant. w = week, m = month

Fig 2. Plasma and synovial fluid concentration of IL-8 and IL-17 in patients treated with L-PRP or HA.

Data are expressed as medians and interquartile ranges; comparisons among time points, as determined by Friedman-ANOVA test, and between L-PRP and HA treatments, as determined by the Mann-Whitney U test, are not significant, excluded the comparison between IL-8 concentration in the synovial fluids at w2, p

Fig 3. Plasma and synovial fluid concentration of IL-4, IL-10 and IL-13 in patients treated with L-PRP or HA.

Data are expressed as medians and interquartile ranges; comparisons among time points, as determined by Friedman-ANOVA test, and between L-PRP and HA treatments, as determined by the Mann-Whitney U test, are not significant. w = week, m = month

Fig 4. Synovial fluid concentration of FGF-b, HGF and PDGF-AB/BB in patients treated with L-PRP or HA.

Data are expressed as medians and interquartile ranges; comparisons among time points, as determined by Friedman-ANOVA test, and between L-PRP and HA treatments, as determined by the Mann-Whitney U test, are not significant. w = week