SURGICAL STRESS INDUCES A SHIFT IN THE TYPE-1 TYPE-2 T-HELPER CELL BALANCE, SUGGESTING DOWN-REGULATION OF CELL-MEDIATED AND UP-REGULATION OF ANTIBODY-MEDIATED IMMUNITY COMMENSURATE TO THE TRAUMA/

Background. Measuring serum cytokines, pituitary hormones, or acute ph ase proteins during or after surgery is not an optimal method for quan tifying the impact of surgical procedures. In an effort to assess surg ical stress by means of the immune response, we focused on changes in cell-mediated and antibody-mediated immunity as illustrated by the typ e 1/type 2 T-helper (Th1/Th2) cell balance. The sensitivity of this ap proach was evaluated by comparing laparoscopic and conventional cholec ystectomy (LCE, CCE). Methods. In a pragmatic prospective study 43 pat ients with symptomatic cholelithiasis were operated on either by LCE ( n = 25) or CCE (n = 18). Blood sampling was done 24 hours before surge ry, immediately before incision, and 2, 24, and 48 hours after surgery . Cell surface markers and cytokine production were used to characteri ze the Th1/Th2 balance and were measured by means of flow cytometry an d enzyme-linked immunosorbent assay techniques. Results. Activation of Th2 cells evokes the production and secretion of interleukin-4 (IL-4) , which up-regulates the expression of immunoglobulin E receptors (F a e RII, CD23) on B cells. Phytohemagglutinin-induced IL-4 production in freshly isolated peripheral blood mononuclear cells from patients inc reased more after CCE than LCE (IL-4, +41% versus +17%; p < 0.05). Als o the expression of CD23 on B cells was higher after CCE than LCE (+14 6% versus +63%; p < 0.01). CD30, a membrane molecule that belongs to t he tumor necrosis factor receptor superfamily and probably is an impor tant indicator of Th2 activity, was more elevated on T cells from pati ents who underwent CCE. The Th1 response, characterized by phytohemagg lutinin-induced IFN-gamma secretion in peripheral blood mononuclear ce lls and up-regulation of human leukocyte antigen-DR expression on mono cytes, was lower after CCE than after LCE. Conclusions. This study sho ws that surgical stress induces a shift in the Th1/Th2 balance toward Th2, suggesting that cell-mediated immunity is down-regulated and anti body-mediated immunity is up-regulated after surgery. The evaluation o f this shift may be clinically meaningful and help quantify even less invasive surgical procedures. When comparing CCE and LCE in this not s trictly randomized study, we found LCE to be the less stressful proced ure.