ALARMINS AND IL-6 RELEASE FOLLOWING FEMORAL NAIL: QUANTIFICATION OF SIRS AND OF THE SECOND HIT

Abstract

Purpose: The role of the pro-inflammatory cytokine HMGB1 (alarmins) has not been investigated in the clinical setting. This study aims to assess its relationship to IL-6 release, ISS, and to quantify the second hit phenomenon after femoral nailing.

Methods: 22 (13 males, mean age 37.5y) consecutive patients were entered into this prospective randomised trial. All patients underwent stabilisation of the femoral shaft fracture with reamed (10 patients) or unreamed nailing. Patient demographics, ISS, and complications were recorded prospectively. Peripheral blood samples were collected on admission, induction of anaesthesia, entry into femoral canal, wound closure and on day 1, 3, and 6. Serum HMGB1 and IL-6 concentrations were measured using ELISAs. 6 healthy volunteers formed the control group.

Results: The median ISS was 14.5 (9–29). Admission median HMGB1 and IL-6 concentrations were 7.2 ng/ml and 169 pg/ml respectively. A direct correlation was observed between ISS and IL-6 concentrations. HMGB1 concentrations reached to peak levels on day-6. On the contrary, the median concentration of IL-6 peaked around day 1 postoperatively (reamed: 780 vs. unreamed: 376 pg/ml) and then showed a downward trend. The median increase of HMGB1 by day 6 was 4.21ng/ml in the reamed and 2.98ng/ml in the unreamed population; the median increase of IL-6 by day 1 measured 462 pg/ml and 232 pg/ml in the respective groups.

Conclusion: Femoral nailing and reaming induces a second hit response as supported by the post-operative increased levels of IL-6. There appears to be an inverse relationship in the concentrations of IL-6 and HMGB-1. Serum concentration of IL-6 unlike HMGB-1 strongly correlate with ISS. While IL-6 has been suggested as a marker of assessment of the early inflammatory response, alarmins can provide useful information at the later stage of an evolving immune-inflammatory process.