Interleukin-1 plays major role in wound healing

Anesthesiologists are playing a leading role in research into the molecular factors affecting inflammation, pain, and healing of surgical incisions, as illustrated by papers published in the December issue of Anesthesia & Analgesia, official journal of the International Anesthesia Research Society (IARS).

The signaling molecule interleukin-1 (IL-1) plays a major role in regulating inflammation in response to wounds, according to studies by an anesthesiology research group at Stanford University. Their findings raise the possibility that using drugs to block the IL-1 receptor might help to control incision pain after surgery. Another Stanford group presents evidence that the common practice of instilling local anesthetics into surgical incisions might lead to increased inflammation—potentially interfering with wound healing.

Interleukin-1 Plays Key Role in Wound Healing
Yajing Hu, Ph.D., and colleagues of in the Department of Anesthesia at Stanford performed a series of in-depth experiments to investigate the role of IL-1 in wound biology. They found that IL-1 triggered the release of other molecules that act as mediators of inflammation in response to skin incisions—thus playing a central role in the complex process of wound healing. Studies in mice showed significant genetic variations in levels of IL-1, which in turn affected the production of inflammatory mediators.

In further experiments, Hu and colleagues showed a drug that blocked the IL-1 receptor decreased the production of various inflammatory mediators while also leading to decreased pain responses. They also found evidence that IL-1 stimulated production of inflammatory mediators by human skin cells. Levels of IL-1 were significantly related to inflammation-promoting molecules in human surgical wounds, as well as in areas of sunburned skin.

The new findings highlight IL-1's role in controlling the skin's inflammatory response to surgical incision, and help to draw a more complete picture of what happens on the molecular level in response to tissue injury. The studies also raise the possibility that IL-1 receptor-blocking drugs—already used for other purposes—might be useful in regulating inflammation and pain from surgical incisions. With further research, "Perioperative administration of an IL-1 inhibitor would represent an important step toward developing novel anti-inflammatory strategies to reduce incisional pain," Hsu and co-authors write.

Could Local Anesthetics Inhibit Wound Healing?
In another study, Dr. Brendan Carvalho and colleagues, also of Stanford University, looked at how a common analgesic technique—instilling local anesthetics into surgical wounds—might affect healing. In a group of 38 women undergoing cesarean section, half underwent instillation of the local anesthetic bupivacaine into the area of the incision. The other half received an inactive placebo.

On analysis of healing responses, bupivacaine produced a significant change in the "local composition of wound mediators." Specifically, levels of the anti-inflammatory mediator IL-10 decreased while levels of a pro-inflammatory mediator called substance P increased. Thus bupivacaine infusion seemed to cause "a disruption of anti-inflammatory mechanisms" in the incision, the researchers write.

Although more research is needed, the results raise the possibility that local anesthetic infusion of surgical incisions could lead to an "overall pro-inflammatory wound response," according to Carvalho and colleagues. They also note that there were no significant differences in pain between the two groups of women, and none had any significant problems with wound healing.

"Anesthesiologists are playing a leading role in investigating the molecular processes underlying surgical wound healing, inflammation, and pain," notes Dr. Steven L. Shafer of Columbia University, Editor-in-Chief of Anesthesia & Analgesia. "Further studies of the body's inflammatory and pain responses to surgical incisions will help reduce post operative pain and wound complications following surgery."