Inhibited early immunologic response is associated with hypertrophic scarring

Abstract

This study aimed to examine changes in the inflammatory response in early hypertrophic compared to normal wound healing. The immune system is thought to be involved in hypertrophic scar formation. However, the exact mechanism and time of onset of the derailment remain unknown. In a prospective observational study, skin biopsies were taken directly postwounding and 3 hours later from patients who had elective cardiothoracic surgery. The skin biopsies were analysed for mRNA, proteins and cells involved in the early inflammatory phase of wound healing. The endpoint was scar outcome (hypertrophic (HTS) or normal (NTS)) at one year after surgery. There were significant differences between the NTS and HTS groups regarding the fold changes of mRNA expression of P-selectin during surgery. Postoperative skin concentrations of inflammatory proteins IL-6, IL-8 and CCL2 were significantly lower in the HTS compared to the NTS group. Also, a trend of higher pre-operative M2 macrophage numbers was observed in the HTS group. Neutrophil numbers increased equally during surgery in both groups. The increase of P-selectin mRNA in hypertrophic wound healing could affect leucocyte migration. The decreased concentrations of inflammatory proteins in hypertrophic wound healing indicate a reduced inflammatory response, which has consequences for the treatment of hypertrophic scarring during the early inflammatory phase. In a conclusion, alterations of wound healing associated with hypertrophic scarring are visible as early as 3 hours postwounding and include a reduced rather than increased inflammatory protein response.

Black, White, and Gray: Macrophages in Skin Repair and Disease

“…Most studies in mice have focused on the early inflammatory stage of wound repair to study macrophage contribution to fibrosis. These studies indicate that early pro-inflammatory macrophages are necessary for normal repair while shifts towards either excessive or reduced pro-inflammatory macrophages are associated with HTS 85–87 . However, the key alterations in macrophages that contribute to scar formation seem to occur after day 13, during the proliferation and remodeling phase 4 .…”

Topical use and systemic action of green and roasted coffee oils and ground oils in a cutaneous incision model in rats (Rattus norvegicus albinus)

“…IL-6 plays an important role at the beginning of the inflammatory response and act as a chemotactic factor for leucocyte recruitment. Butzelaar and colleagues found that lower levels of this cytokine in the early stage of skin wound healing could lead to hypertrophic scar formation [ 34 ]. Our group found higher levels of IL-6 mRNA expressed at the wound site in the animals treated with GCO on days 2 and 4 and with RCO on day 2, and the RCO-treated animals showed better wound healing among all groups of this experiment.…”

Inflammation as an orchestrator of cutaneous scar formation: a review of the literature

“…The authors reported reduced expression of inflammatory genes (including TNFα, IL-1α, IL-1RN, several chemokines, and IL-10) in HTS, but the downregulated genes contained both pro- and anti-inflammatory genes. Similarly, another prospective study compared various parameters of inflammation at a very early time point (3 h post-injury) in patients that healed with normal scarring or HTS [ 38 ] . The authors reported reduced protein levels of IL-6, IL-8, and CCL2 in wounds from HTS patients compared to normal scar patients and suggested that reduced inflammation is associated with HTS formation.…”