The Journal of Bone and Joint Surgery (American). 2009;91:2783-2794.
doi:10.2106/JBJS.H.00989
© 2009 The Journal of Bone and Joint Surgery, Inc.
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Surgical Stress-Induced Immune Cell Redistribution Profiles Predict Short-Term and Long-Term Postsurgical Recovery

A Prospective Study

Patricia H. Rosenberger, PhD1, Jeannette R. Ickovics, PhD2, Elissa Epel, PhD3, Eric Nadler, PhD3, Peter Jokl, MD4, John P. Fulkerson, MD5, Jean M. Tillie, BS6 and Firdaus S. Dhabhar, PhD6

1 Department of Psychiatry, Yale University, New Haven, Connecticut and VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT 06516
2 Departments 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
3 Department of Psychiatry, University of California, 3333 California Street, Suite 465, San Francisco, CA 94143
4 Department of Orthopaedics, Yale School of Medicine, 800 Howard Avenue, P.O. Box 208071, New Haven CT 06520
5 Orthopaedic Associates of Hartford, and University of Connecticut Health Center, 85 Seymour Street, Suite 607, Hartford, CT 06106
6 Department 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: dhabhar{at}gmail.com

Investigation performed at the Department of Orthopaedics and Department of Epidemiology and Public Health, Yale University, New Haven, Connecticut; Department of Psychiatry, University of California San Francisco, San Francisco; and Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California

A commentary by Martin I. Boyer, MD, MSc, FRCS(C), is available at www.jbjs.org/commentary and as supplemental material to the online version of this article.

Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants in excess of $10,000 from NIH-NIAMS RO1-AR-46299. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.

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.


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