In addition to proinflammatory cytokines, anti-inflammatory cytokines have also been shown to be important regulators of wound repair. In particular, the role of IL-10 in the healing response has been studied in some detail. This cytokine is thought to play a major role in the limitation and termination of inflammatory responses. In addition, it regulates growth and/or differentiation of various immune cells, but also of keratinocytes and endothelial cells (190). Based on these activities, a role of IL-10 in wound healing appeared likely.
A. Expression of IL-10 at the Wound Site
Two groups determined the expression pattern of this cytokine in the healing wound. Increased levels of IL-10 mRNA were observed after incisional wounding of mice, with a peak at 60 min after injury (202). Using the same wound model, Sato et al. (237) found two peaks of IL-10 expression after injury: an early peak with a maximum at 3 h after wounding and a second peak at day 3 after wounding. Keratinocytes of the wound epidermis and infiltrating mononuclear cells were identified as the major producers of IL-10 mRNA and protein (237). Interestingly, increased expression of IL-10 was shown to be associated with impaired healing, since the levels of this cytokine were strongly increased in human chronic venous insufficiency ulcers compared with autologous donor wound tissue (165).
B. IL-10 Inhibits Inflammation and Scar Formation
To determine the function of IL-10 in wound repair, neutralizing antibodies to this cytokine were applied to incisional mouse wounds. This treatment demonstrated that endogenous IL-10 inhibits the infiltration of neutrophils and macrophages toward the site of injury as well as expression of several chemokines and proinflammatory cytokines (237). In another study, the role of IL-10 in fetal scarless healing was investigated (162). These investigators wounded embryonic skin from IL-10 null mice that had been grafted to strain-matched adult mice. Wounds to control embryonic skin grafts showed little inflammation and normal restoration of the dermal architecture. However, wounded IL-10 null grafts were characterized by a significantly higher inflammatory cell infiltration and collagen deposition and an adultlike scarring response. These results suggest an important role of IL-10 in regulating the expression of proinflammatory cytokines in fetal wounds, leading to reduced matrix deposition and scar-free healing.