Kinetics of Inflammatory Mediators in the Immune Response to Burn Injury: Systematic Review and Meta-Analysis of Animal Studies

Patrick P. G. Mulder, Carlijn R. Hooijmans, Marcel Vlig, Esther Middelkoop, Irma Joosten, Hans J. P. M. Koenen, Bouke K. H. L. Boekema

Research output: Contribution to journalArticleAcademicpeer-review


Burns are often accompanied by a dysfunctional immune response, which can lead to systemic inflammation, shock, and excessive scarring. The objective of this study was to provide insight into inflammatory pathways associated with burn-related complications. Because detailed information on the various inflammatory mediators is scattered over individual studies, we systematically reviewed animal experimental data for all reported inflammatory mediators. Meta-analyses of 352 studies revealed a strong increase in cytokines, chemokines, and growth factors, particularly 19 mediators in blood and 12 in burn tissue. Temporal kinetics showed long-lasting surges of proinflammatory cytokines in blood and burn tissue. Significant time-dependent effects were seen for IL-1β, IL-6, TGF-β1, and CCL2. The response of anti-inflammatory mediators was limited. Burn technique had a profound impact on systemic response levels. Large burn size and scalds further increased systemic, but not local inflammation. Animal characteristics greatly affected inflammation, for example, IL-1β, IL-6, and TNF-α levels were highest in young, male rats. Time-dependent effects and dissimilarities in response demonstrate the importance of appropriate study design. Collectively, this review presents a general overview of the burn-induced immune response exposing inflammatory pathways that could be targeted through immunotherapy for burn patients and provides guidance for experimental set-ups to advance burn research.
Original languageEnglish
JournalJournal of Investigative Dermatology
Early online date2023
Publication statusE-pub ahead of print - 2023


  • Blood
  • Chemokines
  • Cytokines
  • Growth factors
  • Inflammation

Cite this