Nicotine effect on inflammatory and growth factor responses in murine cutaneous wound healing

Abstract

The aim of the current study was to investigate the effect of nicotine in an experimental mouse model of cutaneous injury and healing responses, during the inflammatory phase of repair. Nicotine injection in full-thickness excisional skin wounds minimally affected inflammatory mediators like TNF, IL-6 and IL-12 while it induced a down-regulation in the expression of growth factors like VEGF, PDGF, TGF-β1 and TGF-β2, and the anti-inflammatory cytokine IL-10. Analysis of wound closure rate indicated no significant differences between nicotine and saline injected controls. In-vitro studies using bone marrow derived macrophages, resident peritoneal macrophages and RAW 264.7 macrophages, indicated that nicotine down-regulates TNF production. Moreover, nicotine was shown to down-regulate VEGF, PDGF and TGF-β1 in both bone marrow derived macrophages and RAW 264.7 cells. Using an NF-κB luciferase reporter RAW 264.7 cell line, we show that nicotine effects are minimally dependent on NF-κB inhibition. Moreover, nicotinic acetylcholine receptor (nAChR) subunit expression analyses indicated that while β2 nAChR subunit is expressed in mouse macrophages, α7 nAChR is not. In conclusion, while skin inflammatory parameters were not significantly affected by nicotine, a down-regulation of growth factor expression in both mouse skin and macrophages was observed. Reduced growth factor expression by nicotine might contribute, at least in part, to the overall detrimental effects of tobacco use in wound healing and skin diseases.

Impact of Smoking Status in Free Deep Inferior Epigastric Artery Perforator Flap Breast Reconstruction: A Multicenter Study

“…Concurrently, numerous previous articles have linked cigarette smoking to tissue necrosis, reduced wound epithelialization, and scarring. 23,[43][44][45] A major strength of this study lies within the large sample size of 3,926 female patients and 4,577 DIEP flap breast reconstructions after malignancies in 22 different German breast cancer centers between January 2011 and January 2019. Patients were divided into two groups according to smoker status.…”

Nicotine impairs intra‐substance tendon healing after full thickness injury in a rat model

“…While nicotine may have direct local effects on tendon healing, it can also have indirect effects through the modulation of cytokines and chemokines, given that nicotine consumption is a systemic disease. Previous literature has suggested that nicotine down‐regulates the expression of growth factors like VEGF, PDGF, TGF‐β1 and TGF‐β2 but has a less significant effect on inflammatory markers like TNF, IL‐6 and IL‐12 . The downregulation in growth factors, coupled with the decreased vascularity, could explain the decreased quantity of tissue formation in the healing tendons.…”

Transdermal Nicotine Application Attenuates Cardiac Dysfunction after Severe Thermal Injury

“…The reason for this ambiguous reaction in inflammatory bowel diseases is still not understood in entirety [ 23 ]. Still nicotine itself is seen doubtfully as an additive aspect in the treatment after burn trauma especially due to described adverse effects on wound healing [ 24 , 25 ]. This points up the importance of further experiments to distinguish the positive anti-inflammatory effects of nicotine from adverse local effects on wound healing.…”