I. Grzelak

Blood cytokine levels rise even after minor surgical trauma.

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 IL1α, IL1β, IL6, IL8, IL10, and IFNγ, 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 IL1α and IL1β 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.

Surgical Trauma Evokes a Rise in the Frequency of Hematopoietic Progenitor Cells and Cytokine Levels in Blood Circulation

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.

Influence of operative trauma on circulating blood mononuclear cells: analysis using monoclonal antibodies

The influence of operative trauma on the quantity and proportion of cooperating mononuclear cells in peripheral blood of patients with stage 0 uterine cancer who underwent hysterectomy was studied using monoclonal antibodies. The percentage of OKM1+ cells (monocytes) had increased on day 1 by 12.4%, on day 3 by 24.8%, and had returned to normal by day 7. The percentage of large OKIa1+ cells (expressing Ia antigen) on day 1 was increased by 186.9%, while on day 3 it had returned to a normal level. There was a decrease on day 1 of the number and percentage of OKT3+ cells (all T lymphocytes) by 17.4%, OKT4+ cells (helper/inducer cells) by 27.9%, OKT8+ cells (suppressor/cytotoxic cells) by 24.6%, and small OKIa1+ cells by 49.4%. The number and percentage of T lymphocytes remained below the preoperative level throughout the observation period. However, the number of helper cells had increased significantly on day 5, while suppressor cells remained below the preoperative level during the entire observation period. The rising ratio of OKT4+/OKT8+ cells reflected the kinetics of recovery of the helper over the suppressor cell population.