Each year, 1.3 million Americans undergo knee surgery, and how quickly they recover depends on many factors, including their age, the severity and location of the injury and pre-existing conditions, such as arthritis. But new research led by Stanford University School of Medicine neuroimmunologist Firdaus Dhabhar, PhD, suggests that how a patient’s immune system responds to the stress of impending surgery may be the strongest predictor of recovery.

The results suggest that simple, inexpensive blood tests performed while patients are on the operating table may help physicians determine how well patients will recover after they leave the hospital.

In a study published online in the Journal of Bone and Joint Surgery (Vol. 91, No. 12), researchers followed 57 patients scheduled to undergo knee surgery. Several days before surgery, patients gave blood samples to establish a baseline count of their lymphocytes, monocytes and neutrophils. On the morning of surgery, the researchers took another sample before patients were anesthetized, looking to see if patients’ anxiety about the surgery would increase the number of those immune cells. A halfhour after surgery, patients gave another blood sample. Based on their previous work, the researchers reasoned that at this later time during the short-term stress induced by surgery, many blood-borne immune cells would exit the circulation and enter tissues at the site of surgery, where they would begin the healing process.

The researchers found that patients whose immune systems responded to the stress of surgery by mobilizing large numbers of pathogen-fighting cells recovered more quickly and completely than patients whose immune cell count before surgery was unresponsive during the short-term stress. They also found that women were less likely than men to mount an adaptive stress response, leading to lower overall knee recovery. Dhabhar is now investigating whether the activation of “fight-or-flight” stress responses might enhance immune system protection in other contexts, such as after receiving a vaccination or during cancer treatment and recovery.

“Our long-term goal is to use these findings to devise pharmacologic and behavioral interventions to manipulate immune cell redistribution during surgery in ways that would maximize healing and recovery,” he says.

—A. Novotney