Severity, Time, and β-Adrenergic Receptor Involvement in Surgery-Induced Immune Alterations

Abstract

Although investigations of surgical stress in animals have reported immune alterations, surprisingly little is known about the variables or mechanisms contributing to the effect. Thus, we completed a series of experiments investigating the immune-altering effects of surgery severity, time of maximal immune alterations, and recovery, as well as the involvement of β-adrenergic receptors in surgery-induced immune alterations in Lewis rats. Immune alterations included natural killer (NK) cell cytotoxicity as well as B- and T-cell proliferation. Results showed increased immune suppression with larger incisions (6 cm > 3 cm > anesthesia > saline). In addition, maximal immune alterations induced by surgery occurred after 24 h; anesthesia effects predominated at the earlier time points. Recovery of immune status varied depending on the immunological measure of interest. Although NK cell cytotoxicity returned to control values within 2 days, B-cell proliferation remained suppressed for at least 8 days, and T-cell proliferation did not begin to recover until 4–8 days following the surgical procedure. To assess the mechanisms involved in surgery-induced immune alterations, follow-up assessments evaluated the effect of nadolol, a β-adrenergic receptor antagonist, on surgery-induced immune alterations. Results show that nadolol blocks the surgery-induced reduction in B- and T-cell proliferation but has no effect on the suppression of NK cell cytotoxicity. These results indicate the need to consider surgical severity and postoperative time of immune assessment when investigating the immune-altering effects of surgery. Importantly, activation of β-adrenergic receptors appears to play a modulatory role in surgery-induced immune alterations.