PLASMA CYTOKINES AND TISSUE GENE EXPRESSION IN A PRE-CLINICA RANDOMISED TRIAL OF EXTREMITY WAR WOUND DRESSINGS

A randomised controlled trial was conducted using a rabbit model of a complex contaminated extremity war wound. Compared to saline soaked gauze dressings Inadine (iodine) and Acticoat (nanocrystalline silver) had significantly lower levels of Staphylococcus aureus after 7 days while Activon Tulle (Manuka honey) had significantly higher levels. Molecular level analysis of the wound was conducted. Plasma cytokines of interest were assayed using ELISA and levels of expression of relevant tissue genes measured using PCR following RNA extraction. Appreciable levels of Interleukins 4 and 6 and Tumour Necrosis Factor-α were identified in plasma with significantly higher levels of IL-4 and TNFα detected in the Activon Tulle group. In tissue TNFα, Matrix metalloproteinase-3 and the ratio of Matrix metalloproteinase-9 to Tissue Inhibitor of Matrix metalloproteinase-1 were significantly higher in tissue injured limbs than the uninjured limbs with no significant differences between groups. Interpretation of these results is challenging. IL-4 has been associated with transition from pathological inflammation to repair and TNFα with impaired healing. However, Activon Tulle had significantly higher levels of S. aureus and we found no differences in observational, histology, haematology or tissue gene expression outcomes over 7 days which would correlate with these molecular biology results.