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Surgical Stress-Induced Immune Cell Redistribution Profiles Predict Short-Term and Long-Term Postsurgical Recovery: A Prospective Study

Rosenberger, Patricia H. PhD; Ickovics, Jeannette R. PhD; Epel, Elissa PhD; Nadler, Eric PhD; Jokl, Peter MD; Fulkerson, John P. MD; Tillie, Jean M. BS; Dhabhar, Firdaus S. PhD

Journal of Bone & Joint Surgery - American Volume: 01 December 2009 - Volume 91 - Issue 12 - p 2783–2794
doi: 10.2106/JBJS.H.00989
Scientific Articles

Background: The experience of undergoing surgery is known to induce a short-term, fight-or-flight physiological stress response. As an optimum immune response at the site of surgery would enhance tissue repair, we examined surgical stress-induced immune cell redistribution profiles as predictors, and potential mediators, of short and long-term postoperative recovery. We tested the a priori hypothesis that predefined adaptive immune cell redistribution profiles observed during surgery will predict enhanced postoperative recovery.

Methods: This prospective longitudinal study involved fifty-seven patients undergoing meniscectomy. Knee function was assessed preoperatively and at one, three, eight, sixteen, twenty-four, and forty-eight weeks postoperatively with use of the clinically validated Lysholm scale, which assesses mechanical function, pain, mobility, and the ability to perform daily activities. Surgery-induced immune cell redistribution was measured in the blood at baseline, before surgery, and after surgery.

Results: Mixed-model repeated-measures analyses revealed a main effect of immune cell redistribution: patients who showed the predefined “adaptive” lymphocyte and monocyte redistribution profiles during surgery showed enhanced recovery. Interesting differences were also observed between the sexes: women as a group showed less adaptive redistribution and correspondingly showed significantly delayed maximum recovery, requiring forty-eight weeks, compared with men, who required only sixteen weeks. Inter-individual differences in leukocyte redistribution predicted the rate of recovery across both sexes.

Conclusions: Immune cell redistribution that is induced by the stress of undergoing surgery can predict (and may partially mediate) postoperative healing and recovery. These findings may provide the basis for identifying patients (either prospectively or during surgery) who are likely to show good as opposed to poor recovery following surgery and for designing interventions that would maximize protective immune responses and enhance the rate and extent of recovery.

Level of Evidence: Prognostic Level I. See Instructions to Authors for a complete description of levels of evidence.

1Department of Psychiatry, Yale University, New Haven, Connecticut and VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT 06516

2Departments of Epidemiology and Public Health and Psychology, Yale School of Public Health, Yale University, 60 College Street, P.O. Box 208034, New Haven, CT 06520

3Department of Psychiatry, University of California, 3333 California Street, Suite 465, San Francisco, CA 94143

4Department of Orthopaedics, Yale School of Medicine, 800 Howard Avenue, P.O. Box 208071, New Haven CT 06520

5Orthopaedic Associates of Hartford, and University of Connecticut Health Center, 85 Seymour Street, Suite 607, Hartford, CT 06106

6Department of Psychiatry and Behavioral Sciences, Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, 300 Pasteur Drive, MC 5135, Stanford, CA 94305-5135. E-mail address for F.S. Dhabhar:

Copyright 2009 by The Journal of Bone and Joint Surgery, Incorporated
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