Alterations in the mononuclear cell populations in the blood circulation are among the most characteristic changes after surgical trauma. They reflect changes in the hematopoietic compartment which develop following surgery. The process of mobilization and differentiation of the hematopoietic population is regulated by cytokines known as growth factors for stem and progenitor cells (SCF, IL-1, IL-3, IL-6, IL-11, TNF, CSFs). Our question was whether operative trauma resulted in the release of the hematopoietic progenitor cells to the blood circulation and an increase in the blood level of cytokines participating in hematopoiesis. The studies were carried out in patients with chronic cholelithiasis, undergoing elective open cholecystectomy under general anesthesia. An increase in the frequency of circulating CD34+ hematopoietic progenitor cells was seen between days 3 and 7 after surgery. Moreover, a significant increase in the percentage of immature cells of myeloid lineage (CD13+, CD14+, CD33+) was seen on the 1st and 3rd postoperative days. This could be the result of an expansion of the total bone marrow cell number after surgery and a subsequent release of these cells into the blood circulation. The changes in blood cell populations were accompanied by an increase in IL-6 on days 1, 3, and 7 following surgery, in IL-6sR on days 10 and 14 and in IL-8 on days 1 and 3. No significant changes in IL-1α, IL-1β, IL-3 and IL-11 were noted. A small rise in GM-CSF was noted in few patients on the 3rd and 7th postoperative days. It is known that IL6 is involved in hematopoiesis, that the IL-6-IL-6sR complex may induce both proliferation and differentiation of hematopoietic progenitor cells and that IL-8 possesses progenitor cell mobilization properties. The appearance of hematopoietic progenitor cells in the blood following surgery may represent a process for the expansion of the immune cell pool after trauma and maintaining of the reserves at a certain level.

The exact changes in cytokine production and clinical implications of the increased cytokine levels following operative trauma remain unclear. In this study, systemic production of a spectrum of cytokines, including IL1 alpha, IL1 beta, IL6, IL8, IL10, and IFN gamma, was examined in patients undergoing minor elective operative trauma. The levels of IL1 receptor antagonist (ra) and IL6 soluble receptor (sR) were also determined. Although there were no changes in IL1 alpha and IL1 beta plasma levels during the entire observation period, there was a significant rise in IL1 ra level in all patients between postoperative day 1 and postoperative day 14. A significant increase in the IL6 plasma level was seen on days 1, 3, and 7 after surgery and an increase in the IL6 sR level was observed on postoperative days 10 and 14. Interestingly, the IL8 plasma values had risen significantly on days 1 and 3 following the operation. In some patients, an elevation in IL10 plasma level was noted on days 1 and 3 postsurgery. Results demonstrated that even a minor surgical procedure such as cholecystectomy with uneventful wound healing was followed by an appearance in the blood circulation of significant levels of cytokines between day 1 and day 14 after surgery. These observations point to the necessity of searching for methods of down-regulating the systemic cytokine effects after surgical trauma for the routine postoperative management.

Massive whole blood transfusion, either syngeneic or allogeneic, constitutes a strong downregulating signal for hematopoiesis, affecting the erythroid, myeloid, and lymphoid cell lineages. It leads also to an attenuation of the responsiveness of hematopoietic tissues to mitogenic stimuli.

The in vitro interleukin-1 (IL-1) and interleukin-2 (IL-2) production and IL-2 receptor (IL-2-R) expression by peripheral blood mononuclear (PBM) cells were examined in patients undergoing elective cholecystectomy. The IL-1 production by monocytes stimulated with a lipopolysaccharide (LPS) did not change on day +1 but increased by 57.5 % on day + 3 (p < 0.05) after surgery, and was normalized on days +5 and +7. The IL-1 production by PBMcells stimulated by LPS increased by 97.6% on day +1 (p < 0.05) and 109.5% on day + 3 (p < 0.05) after surgery, and became normalized on days +5 and +7. The IL-2 level in PBM cell supernatants stimulated with phytohemagglutinin (PHA) decreased by 45.2% on day +1 (p < 0.05), 33.3% on day + 3 (p < 0.05), 32.3% on day + 5 (p < 0.05) and returned to the preoperative values on day + 7. The IL-2-R expression on PHA-stimulated lymphocytes increased from 60.4 ± 4.8% preoperatively to 67.2 ± 1.9% on day +1 (p < 0.05) but was again within the preoperative values on days + 3, + 5 and + 7. In order to detect the described changes, stimulation with PHA had to be used. This indicates that simple surgical trauma produces subthreshold activation of blood immune cells. The cells enter the ‘response alert’ stage which can be measured after stimulation with lectins. A drop in the number of OKT+ cells but also insufficient production of IL-2 by OKT4+ cells for covering the requirements of activated cells may be responsible for the low levels of IL-2 detected after surgical trauma.

The effects of 3 h lasting local hyperthermia on immune cell traffic through the normal human skin to afferent lymphatics, cell phenotypes, responsiveness, and stimulatory properties were studied in eight men. Cells were harvested from lymph drained from foot skin. Heating the skin in a water bath of 44 degrees C (skin temperature 2 mm under the surface 39 degrees C) evoked an augmented traffic of mononuclear cells to lymph with preponderance of large, macrophage-like, Ia-positive cells, among them Langerhans cells. Lymphocytes obtained from the heated skin lymph revealed in cultured increased spontaneous blastic transformation rate, augmented responsiveness to phytohemagglutinin (PHA), and enhanced PHA-presenting properties to autologous peripheral blood mononuclear (PBM) cells. An increased stimulatory activity on allogeneic mixed lymphocyte reaction (MLR) was also observed. Lymph from heated skin augmented the PBM responsiveness to PHA and showed increased interleukin-1-like activity. Local heating of the skin is a potent signal initiating augmented traffic, and enhanced responsiveness and stimulatory activity of "passenger" immune cells. Their rapid nonspecific activation makes them indiscriminately active against a wide range of antigens before the specific response is developed.