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.

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.

A group of 37 patients with nonactive multiple sclerosis and 20 healthy individuals (HI) were examined by the standard lymphocyte transformation test for their blastogenic response to a wide range of concentrations of human myelin basic protein (BP), purified protein derivative of tubercle bacilli and phytohemagglutinin. The group with multiple sclerosis (MS) showed a lower blastogenic response than the group of HI. The suppressed response was dose dependent; the highest suppressor activity was found at a BP concentration of 0.5 μg/ml, lower suppression was noted at a BP concentration of 50 μg/ml and no suppression could be detected when 5 × 10^––7μg of BP/ml was employed. The suppressed response was confirmed using a two-stage procedure based on the concanavalin-A (Con-A) stimulation of the BP-pretreated lymphocytes. In the second-stage cultures, Con-A seemed to induce a clonal expansion of the BP-activated cells. The degree of blastogenic response could be similarly detected with a wide range of concentrations of Con-A. Phytohemagglutinin was not as effective as Con-A in detecting the BP-induced activity. Cultured lymphocytes were as good responders to the BP-induced activity as fresh autologous lymphocytes. The results of comparative studies using both procedures and their effectiveness in detecting the cellular response to BP are discussed.

Peripheral blood lymphocytes from 51 multiple sclerosis (MS) patients and 23 healthy individuals were examined for their response to human myelin basic protein at three concentrations. Cells from active-MS patients responded in most cases with definitely enhanced blastogenic stimulation (BS), whereas those of the nonactive-MS patients or of patients in remission showed values of BS similar to or below those of the control group. Patients and control individuals were divided in two groups according to their age. The younger group included individuals from 20 to 40 years of age, the older those from 41 to 68 years. The lowest and highest values obtained using the three doses of basic protein were selected and the results compared. The higher values of BS and the greater frequency of active blood samples were observed in the younger than in the older active-MS patients. On the other hand, a larger number of samples obtained from the older patients showed the lowest values of BS. The relevance of age to the suppressor activity induced by the basic protein in the lymphocytes of MS patients is discussed.