Hanna Bessler

Effect of pentoxifylline on the phagocytic activity, cAMP levels, and superoxide anion production by monocytes and polymorphonuclear cells.

The effect of pentoxifylline (Trental) on the phagocytic capacity, cAMP levels, and superoxide anion production of human peripheral blood monocytes and polymorphonuclears (PMNs) was studied. The drug inhibited the phagocytosis of latex particles by both monocytes and PMNs in a dose‐dependent manner. In addition, superoxide anion production during the phagocytic process was also reduced following incubation of the cells with pentoxifylline. It is suggested that this inhibitory effect is due to the increased intracellular levels of cAMP induced by the drug.

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.

Platelet Count and Thrombopoietic Activity in Patients with Chronic Renal Failure

The frequency of thrombocytopenia in patients with chronic renal failure (CRF) is controversial. This study was undertaken to investigate the platelet count in 55 patients with end-stage renal disease on maintenance hemodialysis and in 19 patients with CRF before hemodialysis had begun. In both groups platelet counts were similar and significantly reduced, 175,000 +/- 6,500 and 181,000 +/- 10,800 compared to 253,000 +/- 3,700/mm3 in the control (p less than 0.0001). 31% of hemodialysis patients had thrombocytopenia (platelet count less than 150,000/mm3). The megakaryocyte number in their bone marrow aspirate was not reduced. Primary renal disease, androgen treatment or parathyroidectomy did not affect the platelet count. Thrombopoietic activity using 75Se-selenomethionine incorporation into platelets measured in 7 thrombocytopenic patients was found to be reduced, 6.77 +/- 0.29 vs. 9.06 +/- 0.27 (X 10(-2)%: p less than 0.001). This study shows that the platelet count is reduced and mild thrombocytopenia is frequent in patients with CRF. A possible cause for the platelet count reduction is insufficient thrombopoietic activity.

Effect of citrus pectin on malignant cell proliferation

The effect of citrus pectin (CP) on the proliferative capacity of four malignant cell lines was examined. Various dose of CP inhibited the proliferation of two-colon carcinoma and an erythroleukemia cell lines. Raji cells were not affected at all. The three lines affected by CP are known to express galectins which are pivotal for cell growth and metastasis, while Raji cells, whose proliferation was not affected by CP, are deficient of this betagalactoside. It is possible that the antiproliferative effect of CP on the malignant cells may be due at least in part to its ability to inhibit galectin expression.

CD14 receptor expression and lipopolysaccharide-induced cytokine production in preterm and term neonates.

CD14 expression and the capacity of mononuclear cells (MC) from preterm and term neonates to secrete the proinflammatory cytokines interleukin (IL) 1β, tumor necrosis factor α and IL-6 in response to lipopolysaccharide (LPS) was investigated and compared to that of adults. MC were incubated with various doses of LPS, and the cytokine level in the supernatants was tested. CD14 receptors on MC and the intensity of their expression were analyzed. MC of preterm and term neonates and adults responded to LPS with low, medium and high proinflammatory cytokine production, respectively. CD14 expression was lowest in preterm infants, intermediate in term infants and highest in adults. The difference between term and preterm neonates for both parameters was significant. The results suggest a possible correlation between the lower expression of CD14 receptor on neonatal cells and the reduced secretion of proinflammatory cytokines by these cells. This decreased production may possibly contribute to the low ability of neonates to develop fever.

In vitro DNA and RNA synthesis by human platelets.

In vitro incorporation of [Me-3H] thymidine and [5-3H] uridine into human platelets was demonstrated. Thymidine incorporation was inhibited by three specific inhibitors of DNA synthesis: hydroxyurea, cytosine arabinoside and daunomycin. The effect was dose-dependent. Uridine uptake by platelets was found to be inhibited by specific inhibitors of RNA synthesis such as actinomycin D, rifampicin and vincristine, the effect of actinomycin D being dose dependent. The drug also led to a time-dependent inhibition of protein synthesis when preincubated with platelets. The platelet RNA profile on polyacrylamide gel was demonstrated to be similar to that of embryonic mouse erythroblast RNA. Synthesis of all three fractions, 28 S, 18 S and 4 S, was inhibited by actinomycin D. These findings show that human platelets are capable of DNA and RNA synthesis, and that these activities play a role in controlling protein synthesis in these cells. Detectable amounts of DNA have been found in whole human platelets, and in isolated mitochondria derived from these cells. Isolated platelet mitochondria incorporated [3H] thymidine and [3H] uridine into their macromolecules. These activities were inhibited by daunomycin and by both rifampicin and actinomycin D, respectively. These results support the assumption that DNA and RNA synthesis found in intact cell preparations takes place most probably in platelet mitochondria.

In Vitro Effect of Lycopene on Cytokine Production by Human Peripheral Blood Mononuclear Cells

There is evidence indicating that regular consumption of tomato products is associated with favorable immunomodulatory effects. In addition, tomato extracts have been shown to possess antioxidant, anticarcinogenic and antithrombotic activity in vitro. Since tomatoes are rich in carotenoids and particularly in lycopene—the pigment responsible for the red color of tomatoes—the present work was designed to examine the in vitro effect of lycopene on cytokine production by peripheral blood mononuclear cells (PBMC) from 15 healthy subjects. First, 2 × 106 PBMC suspended in 1 ml of conditioned medium were incubated over a period of 24 and 48 hours without or with the following concentrations of lycopene: 0.25, 0.5, 1.0, 2.0 and 4.0 μM. The production of the subsequent cytokines was evaluated: IL-1β, IL-1ra, IL-2, IL‐6 and IL-10, as well as TNFα and IFNγ. Lycopene induced a dose-dependent increase in IL1β, and TNFα production and a decrease in IL-2, IL-10 and IFNγ secretion, whereas that of IL-6 and IL-1ra was not affected. It is concluded that understanding the role of lycopene in modulation of the immune system may promote decisions as for dietary supplementation of lycopene for reducing the risk of certain diseases.

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.

Effect of Dexamethasone on IL-10 and IL-12p40 Production in Newborns and Adults

The effect of dexamethasone (DEX) on interleukin (IL)-10 and IL-12p40 production was examined in preterm newborns, term infants and was compared to that in adults. Mononuclear cells isolated from newborn cord blood (CBMC) and peripheral blood from adults (PBMC) were incubated with lipopolysaccharide in the absence or presence of DEX at concentrations between 10–8 and 10–5 M. Cytokine concentration in the supernatants was tested using ELISA kits. DEX induced a dose-dependent inhibition of IL-10 production by PBMC from adults whereas CBMC from newborns were mostly unaffected by the drug. DEX caused a dose-dependent inhibition of IL-12p40 secretion by cells of the three age groups, although to a different extent. Since IL-12 plays a critical role in the development of a protective immune response to fungal infection, it is conceivable that the inhibition of IL-12p40 secretion caused by DEX may contribute to the increased occurrence of fungal infections in preterms treated with this drug.

On the mechanism of post-splenectomy leukocytosis in mice.

Background  Increased number of peripheral white blood cells (PWBCs) has been noted after removal of the spleen.