Immunomodulatory effect of Manuka honey on macrophage polarisation and its impact on acute wound healing: An experimental study in Swiss albino mice.

Abstract

Background and objectives Manuka honey promotes wound healing through antimicrobial and immunomodulatory actions, but its effect on the temporal dynamics of macrophage polarisation (M1→M2 switch) in acute wounds is poorly characterised. The primary objective was to compare the percentage reduction in wound size (wound healing rate) between Manuka honey and control groups; secondary objectives were to compare histopathological healing parameters and tissue cytokines (IL-1β, IL-10, and the IL-1β:IL-10 ratio) as surrogate markers of macrophage polarisation. Methods Thirty male Swiss albino mice (8-12 wk; 25-30 g) were randomised equally to Manuka honey (test) or saline (control), with two dorsal full-thickness wounds (1.0 cm) per animal treated daily for 10 days. The primary outcome was wound healing rate (WHR; % reduction in wound area from day 0 to day 10; a continuous variable measured by ImageJ planimetry). Secondary outcomes were histopathological parameters (inflammatory cell density, neutrophils, eosinophils, oedema, granulation tissue, fibroblast density and activation, epithelialisation, keratinisation), scored as categorical variables, and tissue IL-1β and IL-10 measured by ELISA, on days 5 and 10. Continuous variables were compared using Student's t-test and categorical variables using the Chi-square/Fisher's exact test; P<0.05 was considered significant. Results The test group achieved a higher WHR at day 10 (77.3±5.9% vs. 69.6±5.1%; P=0.003). Histologically, granulation tissue was greater on day 5 (P=0.037); by day 10, neutrophils (P=0.016) and oedema (P=0.038) were reduced, while fibroblast density (P=0.010) and activation (P<0.001) increased. Cytokines were comparable on day 5; by day 10 the test group had lower IL-1β (44.33±11.37 vs. 56.38±16.10 ng/mL; P=0.034), higher IL-10 (17.89±3.15 vs. 14.58±3.87 ng/mL; P=0.022), and a lower IL-1β:IL-10 ratio (3.02±1.90 vs. 4.02±1.46; P=0.044). Interpretation and conclusions Manuka honey accelerated acute wound healing, increasing the wound healing rate alongside an earlier M1→M2 macrophage shift - reflected in lower pro-inflammatory and higher anti-inflammatory cytokines and improved histological repair - supporting its therapeutic potential in wound management.