Effects of propofol emulsion and thiopentone on T helper cell type-1/type-2 balance in vitro.

We have earlier found increased percentages of T helper cells (CD4-positive lymphocytes) in the blood circulation after propofol infusion anaesthesia. Cytokines interferon-gamma (IFN gamma) and interleukin-4 (IL-4) are important in the differentiation of T helper cells into subtypes T helper type-1 (Th1) and type-2 (Th2). To study the effects of propofol emulsion, its solvent Intralipid and thiopentone on Th1/Th2 balance, measurements of IFN gamma and IL-4 production by mononuclear leucocytes were carried out in vitro. As IL-2 has a central role in immune responses to surgery, its production was also measured. Concanavalin A-stimulated mononuclear cells were cultured in the presence of propofol emulsion at 3.5 or 10 micrograms.ml-1, Intralipid 35 or 100 micrograms.ml-1, or thiopentone 3 micrograms.ml-1. Cytokine production was measured from the conditioned media of mononuclear cell cultures. Decreased IFN gamma (p < 0.001) and IL-4 concentrations (p < 0.01) were found in the presence of thiopentone, but IL-2 production was unaffected. By contrast, propofol emulsion or Intralipid had no effects on IFN gamma, IL-2 or IL-4 concentrations. Propofol 10 micrograms.ml-1 increased the IFN gamma/IL-4 ratio from the control value median 243 (162-562) (25th-75th percentile) to 363 (195-1028) (p < 0.01), but thiopentone decreased it to 145 (60-214) (p < 0.01). These findings show that propofol and thiopentone have different effects in vitro on Th1/Th2 balance and suggest that they have different modulating effects on the immune response.

Propofol infusion anaesthesia and the immune response in elderly patients undergoing ophthalmic surgery.

In our earlier studies, propofol infusion anaesthesia increased the percentage of T helper cells in middle-aged surgical patients undergoing minor or major surgery. In the present study we compared the effects of total intravenous propofol anaesthesia and combined isoflurane anaesthesia on the immune response to ophthalmic surgery in elderly patients. Twenty patients (median age 75 years, ASA 2-3) were randomly allocated to receive total intravenous propofol anaesthesia (median total dose of propofol 710 mg) or combined isoflurane anaesthesia (median end-expiratory concentration of isoflurane 0.45 vol %). The following were measured pre-operatively, at the end of operation and on the first postoperative morning: leucocyte and differential counts: percentages of lymphocyte subpopulations (CD3, CD4, CD8, CD20, CD16) and monocytes (CD14); phytohaemagglutinin-, concanavalin A- and pokeweed mitogen-induced and unstimulated lymphocyte proliferative responses: polyclonal immunoglobulin synthesis as well as serum cortisol concentrations. The immune response to ophthalmic surgery was basically similar in both anaesthetic groups. The percentage of T helper cells in the blood circulation increased in the propofol group (p < 0.05) but not in the isoflurane group. The difference in the time-response profile for T helper cell percentages between the groups was also statistically significant (p < 0.01).

The influence of anaesthetic technique upon the immune response to hysterectomy. A comparison of propofol infusion and isoflurane.

Earlier studies on propofol have shown increased percentages of T helper cells after minor surgery. In this study, the effects of propofol infusion anaesthesia on the immune response were compared with those of combined isoflurane anaesthesia in 30 patients (median age 47 years, ASA 1-2) undergoing major surgery. The total dose of propofol in the propofol infusion group of 15 women was 860 mg (range 540-1520 mg) and the median end-expiratory isoflurane concentration in the combined isoflurane group of 15 women was 0.6% (range 0.5-0.8). The following were measured; leucocyte and differential counts; percentages of lymphocyte subpopulations (CD3, CD4, CD8, CD19, CD16 and HLA-DR+CD3); phytohaemagglutinin-, concanavalin A-, and pokeweed mitogen-induced and unstimulated lymphocyte proliferation; plasma interleukin-6; serum group II phospholipase A2, C-reactive protein and cortisol concentrations. Measurements were made pre-operatively, at the end of the operation and on the first and fifth postoperative days. No statistically significant overall differences were observed in the immune response between the groups. The serum cortisol response was weaker in the propofol group than in the isoflurane group (p < 0.05). Time-related changes were seen within the groups.

Effects of propofol and Intralipid on immune response and prostaglandin E2 production.

The present study evaluated the effects of propofol and its solvent Intralipid on the immune response and in vivo prostaglandin E2 production in patients during induction of anaesthesia and in healthy volunteers after Intralipid injection. Fifteen female patients (median age 48 years, ASA 1-2) scheduled for uterine dilatation and curettage were randomly assigned to two groups. In group 1 propofol (median dose 3.1 mg.kg-1) and in group 2 thiopentone (median dose 6.0 mg.kg-1) were injected intravenously over 60 s. Surgery was started after collection of the last blood sample. In the second part of this study, Intralipid 10% 0.3 ml.kg-1 was injected intravenously in eight healthy volunteers (four women and four men, median age 32 years) over 60 s. Plasma bicyclo-PGE2 concentrations increased during anaesthesia induction in both anaesthetic groups (p < 0.01). By contrast, no changes were seen in plasma bicyclo-PGE2 concentrations after Intralipid injection in volunteers. Lymphocyte proliferative responses to mitogens did not change during anaesthesia induction in patients. In volunteers, Intralipid injection caused a slight increase in T-cell percentages (p < 0.01) and unstimulated lymphocyte proliferative responses (p < 0.05), but it did not affect other lymphocyte subsets and immunoglobulin production. Intralipid and propofol were not found to be immunosuppressive at clinical doses used during anaesthesia induction.

Effects of cardiopulmonary bypass on lymphocytes and their subset counts with or without use of autotransfusion devices.

Lymphocytes and their subset counts were determined in 30 cardiac surgery patients during cardiopulmonary bypass (CPB) with or without use of an autotransfusion device. In the autotransfusion group, centrifuged and washed autologous red blood cells (median 400 mL [range 200-770 mL]) and in the control group corresponding amounts of homologous packed red blood cells (median 500 mL [range 250-750 mL]) were transfused after declamping the aorta. The percentages of T lymphocytes (CD3) and T cytotoxic cells (CD8) increased in both groups (CD3 up to 5%, P < 0.05 and CD8 up to 35%, P < 0.01), but the percentage of T helper cells (CD4) did not change. The ratio of CD4/CD8 cells decreased (up to 34%, P < 0.01). The percentage of naive resting T cells (CD45RA) increased slightly (up to 8%, P < 0.05) whereas the percentages of memory T cells (CD45RO), T cells with IL-2 receptor (CD25), and natural killer cells (CD16) remained unaltered. The percentage of HLA-DR positive lymphocytes increased during CPB (up to 18%, P < 0.05), but it was decreased thereafter (up to 16%, P < 0.05). The percentage of monocytes (CD14) decreased first during CPB in both groups (up to 32%, P < 0.01), but it was higher in the autotransfusion device group (decreased 29% from initial value) than in the control group (decreased 65% from initial value) at the end of CPB (P < 0.05). This study shows that extracorporeal circulation has an effect on lymphocytes and their subset counts. The changes were slightly immunosuppressive. By contrast, use of autotransfusion devices had only minor effects.

Propofol infusion anaesthesia and immune response in minor surgery.

This study was set up to evaluate the effects of propofol infusion anaesthesia on immunological function in minor surgery. Twenty-seven patients (median age 51 years, ASA 1-2) scheduled for minor breast surgery were randomly assigned to two groups. Anaesthesia was induced in group 1 with propofol 2.5 mg.kg-1 and maintained with propofol 12 mg.kg-1 x h-1 and 30% O2 in air, whereas in group 2 anaesthesia was induced with thiopentone 4 mg.kg-1 and maintained with 70% N2O in O2. Fentanyl and vecuronium were used in both groups. The percentages of T cells (p < 0.001), B cells (p < 0.01) and memory T cells increased (p < 0.01) in both groups. T helper cell percentages increased in the propofol but not in the thiopentone group (p < 0.05). The percentages of natural killer cells decreased from pre-induction values in both groups (p < 0.001). No changes were seen in lymphocyte proliferative responses. Minor breast surgery under propofol or conventional combined anaesthesia had only minor effects on the immune response. The higher percentage of T helper cells after propofol anaesthesia compared to conventional combined anaesthesia is beneficial, but its clinical importance remains to be determined.

Propofol emulsion reduces proliferative responses of lymphocytes from intensive care patients.

OBJECTIVE: To test propofol lipid emulsion formulation for its immunosuppressive effects. DESIGN: Propofol lipid emulsion and the emulsion alone were tested at increasing concentrations and compared to initial values and between each other. Propofol alone could not be tested due to its insolubility into the culture medium. PATIENTS AND PARTICIPANTS: Lymphocytes from 12 surgical intensive care (ICU) patients (median APACHE score 16 and median TISS score 28) and 12 healthy volunteers. MEASUREMENTS: Phytohaemagglutinin-, concanavalin A- and pokeweed mitogen-induced lymphocyte proliferative responses were measured in the presence of increasing concentrations of propofol lipid emulsion formulation or the lipid emulsion. RESULTS: Lymphocyte proliferative responses from ICU patients were in general on a lower level than in the volunteers. The propofol lipid emulsion formulation (Diprivan) decreased pokeweed mitogen-induced proliferative responses of lymphocytes from ICU patients at propofol concentrations found in the circulation (1-10 micrograms/ml) and the lipid emulsion alon at 100 micrograms/ml triglyceride concentrations while the other mitogen-induced responses were not affected. No changes were observed in the mitogen-induced responses of lymphocytes from healthy volunteers. CONCLUSIONS: Propofol emulsion formulation decreased in surgical intensive care patients pokeweed mitogen-induced lymphocytic responses in vitro at clinically found concentrations, indicating the need for further studies to test B-lymphocyte functions and T-B-lymphocyte co-operation during propofol lipid emulsion administration. (ICU) patients is widespread because of its good control of sedation. Propofol is currently administered in fat emulsion which is considered immunosuppressive during bolus injection or rapid infusion. Therefore, effects of a propofol fat emulsion formulation on proliferative responses of lymphocytes were studied in blood samples obtained from healthy volunteers and ICU patients known to be immunosuppressed.