IL-1 Plays a Critical Role in Oral, But Not Dermal, Wound Healing

Abstract

Wound healing is a well-orchestrated complex process leading to the repair of injured tissues. After injury, proinflammatory cytokines act as important modulators of the inflammatory process. IL-1 expression has been regarded as necessary for healing; however, its effects have also been implicated in delayed wound repair. Currently, there is no consensus or direct evidence that IL-1 activity plays a central role in the healing process. The present investigation was undertaken to define the role of IL-1R signaling in the healing outcome of an excisional wound in the palate or scalp of mice that had targeted deletions of the IL-1R type 1 (IL-1R1−/−) compared with matched wild-type mice. Histomorphometric analysis was undertaken to assess the degree of healing and the recruitment of polymorphonuclear and mononuclear phagocytes. After 14 days, wild-type mice exhibited complete closure of intraoral wounds, while IL-1R1−/− animals had only partial closure (50%). In the IL-1R1−/− mice, healing tissues exhibited a persistent inflammatory cell infiltrate, which did not occur in wild-type animals. Treatment with antibiotics significantly diminished the persistent inflammatory infiltrate and improved healing in the experimental animals. In contrast to oral wounds, the rate of healing and recruitment of polymorphonuclear cells in scalp wounds was similar in IL-1R1−/− and wild-type mice. The present data underscore the importance of IL-1 in wound healing in a challenging environment and identify its principal role in facilitating the healing process by protecting an open wound from bacterial insult. In a less challenging environment, the production of new connective tissue and its coverage by migrating epithelium are minimally affected by the absence of IL-1 activity.

Increased interleukin 1 and tumor necrosis factor alpha levels after thyroid surgery

“…These factors have the ability to stimulate the release of other cytokines, the promotion of angiogenesis, and production of extra-cellular matrix in the wound healing process after surgery. IL-1 and TNFα have been shown to be essential in the early phases of wound healing (14,(25)(26)(27). In this study, we found increased levels of both IL-1 and TNFα on postoperative day 1, in the early phase of wound healing.…”

Short- and Long-Term Effects of IL-1 and TNF Antagonists on Periodontal Wound Healing

“…Nathan (9) showed that TNF was involved in the late phase of wound healing, in switching from the tissue-damaging mode to the tissue repair-promoting mode after debris and dead cells were no longer present. Another explanation is that IL-1 might play an essential role in antibacterial defense in a challenging environment in which microflora are deleterious to the wound-healing process (17). As a result, the early improvement of periodontal healing has been lost in animals treated long-term with IL-1 and TNF soluble receptors compared with the untreated animals.…”

“…IL-1 can induce apoptosis (14) or antagonize apoptosis through activation of NF-B depending on the cell type (15). A small amount of IL-1 is necessary for host defense and wound healing (16), particularly in a challenging environment (17), whereas overproduction of IL-1 can hinder the early phase of wound healing (18,19). Two primary IL-1Rs (IL-1RI and IL-1RII) have been identified.…”

Intra-articular Anakinra for the Treatment of Persistent Inflammation and Arthrofibrosis following Anterior Cruciate Ligament Reconstruction

“…IL-1 knockout mice demonstrated poor healing of oral wound compared to controls, but dermal wound healing is unaffected. 27 Similarly, increased IL-1 concentration has been associated with poor healing of skin in mice. 28 Thus, elevated levels of IL-1 seem to be detrimental to healing, so blockade of IL-1 may be advantageous postoperatively.…”