Ida Notti

Effects of anesthesia based on large versus small doses of fentanyl on natural killer cell cytotoxicity in the perioperative period.

Surgical stress and general anesthesia suppress immune functions, including natural killer cell cytotoxicity (NKCC).This suppression could be attributable, at least in part, to opiates. We have previously shown that large-dose fentanyl administration suppressed NKCC in rats. The present study sought to compare the effects of two anesthetic protocols, based on large-(LDFA) versus small (SDFA)-dose fentanyl anesthesia on NKCC in the perioperative period. Forty patients were included in this study; half were assigned to each protocol of anesthesia. In each anesthetic group, half the patients were undergoing surgery for malignant diseases, and half for benign conditions. Blood samples were collected during the perioperative period. NKCC was assessed using the chromium release assay. Initially, both types of anesthesia similarly suppressed NKCC, with a peak effect 24 h after surgery. The two types of anesthesia, however, differed in the rate of recovery of NKCC suppression. By the second postoperative day, NKCC returned to control values in the SDFA patients, whereas NKCC was still significantly suppressed after LDFA. These results indicate that LDFA causes prolonged suppression of NK cell function. Whether this suppression might have a long-term impact on the overall outcome, especially in cancer patients, remains to be determined. (Anesth Analg 1996;82:492-7)

Cytokine production in major depressed patients before and after clomipramine treatment

Cytokine production by peripheral blood mononuclear cells (PBMC) was assessed in 10 major depressed patients (5 men and 5 women) before and after 4 weeks of clomipramine treatment and in age- and gender-matched healthy controls. A significant reduction in interleukin-1B (IL-1B), interleukin-2 (IL-2) and interleukin-3-like activity (IL-3-LA) was observed in untreated depressed patients when compared to controls. IL-1B and IL-3-LA synthesis was significantly increased after drug treatment. The suppression of cytokine production by PBMC in depressed patients may be attributed to the depression per se, or it may be related to depression-associated hyperactivity of the hypothalamic-pituitary-adrenal axis. The mode of interaction between depression and cellular immune function and the mediators responsible for the reduced cytokine production need to be studied further.

Immunomodulatory effect of peripheral benzodiazepine receptor ligands on human mononuclear cells.

Immunomodulatory effect of ligands active at the peripheral benzodiazepine receptor (PBR) was examined in human peripheral blood mononuclear cells (PBMC). Ro5-4864, PK11195 and diazepam suppressed phytohemagglutinin (PHA) and concanavalin A (ConA) induced proliferation of PBMC. All three ligands inhibited interleukin-3-like activity (IL-3-LA) secretion, while the production of interleukin-2 (IL-2) was inhibited by Ro5-4864 and diazepam only. The selective central benzodiazepine ligand clonazepam did not affect the cellular immune functions examined. Our results indicate an in-vitro immuno-suppressive activity of peripheral and mixed, but not central type benzodiazepine ligands.

Cytokine production in anorexia nervosa.

The capacity of peripheral blood mononuclear cells (PBMCs) of anorexia nervosa (AN) patients to produce interleukin-1 (IL-1), interleukin-2 (IL-2), and interleukin-3-like activity (IL-3-LA) was studied. A significantly lower (-49%, p < 0.005) capacity to synthesize IL-2 and an almost significantly impaired ability (-35%, p = 0.058) to release IL-3-LA by PBMCs of AN patients was found, as compared with cells of the control group. IL-1 production, either spontaneous or after stimulation with lipopolysaccharide (LPS), did not differ significantly between AN patients and healthy subjects. The lessened capacity to produce IL-2 was accompanied by an enhanced stimulatory activity of the patient sera on the production of this cytokine by PBMCs of healthy subjects. It is therefore suggested that the serum of AN patients contains a stimulatory factor or factors for cytokine production that compensates for the lower production of cytokines by AN PBMCs. Such a compensatory mechanism may explain why AN patients do not have an higher susceptibility to infections.

Cytokine production in obsessive-compulsive disorder

Cytokine production was previously demonstrated to be reduced in untreated major affective patients. In addition, recovery from depression following clomipramine (CMI) treatment was accompanied by the restoration of interleukin-1 beta (IL-1 beta) and interleukin-3-like activity (IL-3-LA) to normal range. In the present study we assessed the in vitro production of IL-1 beta IL-2, and IL-3-LA by peripheral blood mononuclear cells (PBMC) in 11 nondepressed patients with obsessive compulsive disorder (OCD) before and after 8 weeks of CMI treatment. Results were compared with those of 11 healthy subjects. CMI treatment induced a significant improvement in OCD symptoms. No alteration was observed in cytokine production in OCD patients before treatment as compared to control subjects. Moreover, 8 weeks of drug treatment had no effect on cytokine production. In conclusion, OCD per se, as well as CMI treatment, have no effect on interleukin production as measured in this study.

Human colostrum stimulates cytokine production.

The effect of human colostrum on the production of IL-1, IL-3 and IL-6 by peripheral blood mononuclear cells (PBMCs) has been investigated. The aqueous phase of human colostrum significantly stimulated the production of these three cytokines. These findings show the importance of breast feeding not only as a well-balanced nutrient supply but also as a source for growth-promoting factors. It is suggested that the enhanced secretion of IL-1, IL-3 and IL-6 induced by human colostrum may compensate for the lower capacity of neonatal PBMCs to produce these cytokines. It is also possible that, by stimulating the secretion of these cytokines, breast feeding may provide an additional mechanism for the regulation of the neonatal immune system and hematopoiesis.

IL-1β and IL-3-like activity in preterm infants

The capacity of peripheral blood mononuclear cells (PBMC) of pretert ntieonaies lo release I L‐ l /f and IL‐3‐like activity (IL‐3‐LA) has been investigaied. In the present study it was found that this capacity is significantly lower than that of their mothers and or eontrol adults. In addition, the results showed that preterm serum has a lower stitnulatory effect on IL‐1β production and an inhibitory effect on IL‐3‐LA secretion by PBMC of adult controls, in comparison with maternal and adull sera. These findings suggest an additional Teedback mechanism for control of hacmatopoiesis in premature neonates. It is possible that the lower production of IL‐1β and IL‐3‐VLA may be involved in the increased susceptibility to infections of preterm newboms.

Quantitative Determination of Human Plasma Erythropoietin Using Embryonic Mouse Liver Erythroblasts

An in vitro bioassay for the quantitative detection of erythropoietin (Ep) in human plasma is described. The method is based on the increased 3H-uridine incorporation into 12-day embryonic mouse liver erythroblasts due to Ep. It was found that 11 out of 12 anaemic patients showed high plasma Ep level, while 7 out of 8 patients suffering from polycythaemia revealed low Ep values. In 4 out of 8 patients with chronic renal failure the Ep level was within the normal range, whereas in the remaining 4 it was higher than normal. The relative simplicity of the method and the reproducibility of the results make it useful even in the routine laboratory.

Transfer of Iron-Dextran Across the Placenta

In pregnant mice. 55Fe-labeled iron-dextran (Imferon) is transferred across the placenta. It was detected in the bone marrow, liver, spleen and peripheral blood of the pregnant animal, as well as in the embryonic liver erythroid precursors and peripheral blood. Uptake by liver and peripheral blood cells of pregnant anemic mice and by liver erythroid precursors of anemic embryos was significantly higher than in normal control animals. Electron-microscopic examination revealed that the iron deposits in the embryonic liver erythroid precursors had the same structure as the injected Imferon.

Pattern of Liver Erythropoiesis in Embryos of Polycythemic Mice

Polycythemia induced by hypoxia in pregnant mice caused a marked reduction in the total number of erythroid precursors in the 10th, 11th, and 12th day embryonic livers, as compared with controls. In addition, the maturation of the erythroid precursors in the 11th day embryonic livers of polycythemic mice was markedly inhibited in comparison with that of controls, whereas on the following days of gestation the erythropoiesis in embryonic livers of both polycythemic and control mice exhibited a similar pattern. It is suggested that the reduced erythropoiesis in the 11th day embryonic liver of polycythemic mothers provides a stimulation for embryonic erythropoietin production. Subsequently, it triggers the maturation of progenitor erythroid cells in the livers and induces an increased erythropoietic activity in the plasma of 12th and 13th day pregnant polycythemic mice as was observed in our previous study.