Hertzel Salman

IL-1β, IL-2, IL-6 and TNF-α production by peripheral blood mononuclear cells from patients with Parkinson's disease

Summary The capacity of peripheral blood mononuclear cells (PBMC) from patients with treated Parkinsons disease (PD) to produce interleukin (IL) IL-1β IL-2, IL-6, tumor necrosis factor (TNF)-α and the proliferative response to mitogens, was compared with that from cells from healthy subjects. The production of IL-2 and the mitogen response were significantly lower in PD patients, whereas the secretion of IL-1β, IL-6 and TNF-α were significantly enhanced. To evaluate the role of levodopa in creating immunological alterations, PBMC of patients and controls were incubated with concentrations of the drug extrapolated from those used in clinical practice. Levodopa caused an inhibition of mitogen-induced proliferation, stimulation of IL-6 and TNF-α production, whereas the secretion of IL-1β and IL-2 was not affected. The results of the study provide a further support for the interrelationship between the central nervous and immune system. In addition, the data indicate that the immunological alterations found in PD may be partially attributed to levodopa administration.

Citrus pectin affects cytokine production by human peripheral blood mononuclear cells.

Dietary fibers, including pectin, have been shown to exert a favorable effect on a wide spectrum of pathological conditions. Their positive influence on human health is explained by their anti-oxidative, hypocholesterolemic and anti-cancerous effects. However, little has been reported about their activity on the immune system. Therefore, the present study was undertaken to examine the effect of citrus pectin (CP) on cytokine production by human peripheral blood cells (PBMC). PBMC were incubated without or with CP at different degrees of esterification (DE) (approximately 30, approximately 60 and approximately 90% esterified pectin, assigned as DE30, DE60 and DE90, respectively) for detection of IL-1 beta, IL-1 ra, TNFalpha, IL-6 and IL-10 secretion. Incubation with DE60 and DE90 induced a dose-dependent inhibition of the pro-inflammatory cytokine IL-1 beta secretion, whereas D30 did not affect this function. However, CP at all three esterification degrees did not alter the secretion of the additional pro-inflammatory cytokines examined, i.e. TNFalpha and IL-6. Conversely, CP at DE60 and DE90 caused a dose-dependent increased secretion of the anti-inflammatory cytokines IL-1 ra and IL-10, whereas D30 did not affect the production of IL-1 ra and decreased that of IL-10. The findings indicate that CP possesses the capacity to exert an immunomodulatory response in human PBMC which may have a favorable effect on human health.

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.

Ultrastructure of mouse striated muscle fibers following pravastatin administration.

To examine the effect of pravastatin administration on striated muscle ultrastructure, 10 BalbC mice were given pravastatin 40 mg/kg/day for 3 weeks. At the end of the study, blood was withdrawn for evaluation of the serum creatine phospho-kinase (CPK) level and the muscles of the hind legs, as well as the heart and liver of the animals were examined with a light and transmission electron microscope. After treatment with pravastatin the results showed a 101% increase in serum CPK level in comparison to untreated controls. Hematoxillin-eosin stained tissues of pravastatin treated mice did not show any abnormal findings. While the ultrastructure of the heart and liver of the treated animals appeared normal, the muscle fibers showed a marked alterations of the mitochondria, which were increased in size compared to those of the controls. The cristae were heavily damaged and even completely destructed, giving the mitochondria appearance of empty vacuoles. The findings are in favor of a specificity of pravastatin for striated muscles.

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.

Effect of sodium thiopentone anesthesia on the phagocytic activity of rat peritoneal macrophages

To elucidate the effect of sodium thiopentone anesthesia on the function of phagocytic cells, albino rats were anesthetized with 60 mg/kg. of sodium thiopentone. After 90 min., peritoneal macrophages were harvested and their capacity for superoxide anion generation was detected. Following anesthesia for 90 min. latex particles were injected intraperitoneally, and after additional 30 min. the macrophages were derived, embedded in agar and the number of cells engaged in phagocytosis, as well as the number of latex particles engulfed by each individual cell were counted in semi-thick sections. Macrophages of anesthetized animals showed a statistically significant decrease of both superoxide anion generation and mean number of phagocytic cells, and engulfed fewer particles than those of the controls. Similar results were obtained following incubation of the cells with sodium thiopentone in vitro. The serum corticosterone level in anesthetized rats was significantly higher than that of the control animals. The results indicate that impaired phagocytosis following anesthesia induced by sodium thiopentone, in addition to alterations of the immune system caused by surgical trauma, may be one of the reasons for increased susceptibility to infections of surgical patients during the postoperative period.

Caffeine Alters Cytokine Secretion by PBMC Induced by Colon Cancer Cells

Background: Studies have shown that caffeine might be capable to prevent colon cancer development. This activity is linked in part to its anti-inflammatory properties mediated through modulation of immune responses. It was the aim of the study to evaluate the role of caffeine in the immune balance between peripheral blood mononuclear cells (PBMC) and those of HT-29 and RKO human colon cancer lines. Methods: Cytokine production was evaluated following incubation of the two types of cancer cells without and with three concentrations of caffeine. Results: A concentration-dependent inhibition of TNFα and IFNγ secretion by PBMC was observed only after their stimulation by cancer cells. Reduction of the anti-inflammatory IL-1ra and IL-10 production was observed using higher caffeine concentrations only. Conclusion: We presume that by changing the equilibrium between pro- and anti-inflammatory cytokines in favor of anti-inflammation, caffeine may reduce the inflammatory process with a consequent suppression of colorectal cancer progress.

Decreased phagocytic function in patients with Parkinson's disease

To determine the phagocytic function of the peripheral blood polymorphonuclears from patients with treated and untreated Parkinsons disease (PD), these cells were incubated with latex particles and the number of phagocytes, as well as the number of particles engulfed by each individual cell, were counted. Cells of untreated PD patients were significantly less phagocytotic than those of matched subjects without neurological or immune disorders (24% vs. 45%, P < 0.001). In addition, phagocytes from PD patients engulfed less particles per cell than those of the controls (8.4 +/- 0.7 vs. 16.5 +/- 1.3, P < 0.001). There was no significant difference in both functions in untreated and treated PD. The results indicate that in addition to the known immune alterations in patients with PD, the ability of their peripheral blood phagocytic cells to engulf latex particles is impaired.

A Simple Method for Evaluation of Latex Phagocytosis by Rat Peritoneal Macrophages

A Simple Method for Evaluation of Latex Phagocytosis by Rat Peritoneal Macrophages M. Meir Djaldetti H. Hertzel Salman M. Michael Bergman R. Rachel Straussberg S. Svetlana Alexandrova H. Hanna Bessler Laboratory for Hematology Research and Department of Medicine ‘C’, Rabin Medical Center, Golda Campus (Hasharon), Petah Tiqva, Department of Pediatrics ‘C’, Schneider Children Medical Center of Israel, Petah Tiqva, and, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

Effect of diazepam on the immune response of rats exposed to acute and chronic swim stress

To examine the effect of the anti-stress agent diazepam on the immune response, rats were exposed either to acute swim stress, i.e., swimming once only for 30 minutes (non-trained swimmers), or to chronic stress with gradual progressive training for 6 weeks (trained swimmers). Both groups of animals were divided into subgroups treated before swimming with and without diazepam, 1 mg/kg, administered i.m. The phagocytic capacity and superoxide anion generation of the peritoneal macrophages was examined. In addition, the proliferative response of the splenic cells (splenocytes) to concanavalin A (Con A) and phytohemagglutinin (PHA), as well as the serum corticosterone levels were investigated. Diazepam abolished increased superoxide anion production in both non-trained and trained swimmers. In non-trained swimmers, the number of latex particles internalized by each cell was decreased and further reduced by the drug. In trained rats treated with diazepam, the percentage of phagocytosing cells remained reduced compared to controls, whereas the drug prevented a decrease in the engulfing capacity of individual cells. Diazepam lowered the suppressed proliferative response of the splenocytes to PHA found in non-trained swimmers. It is concluded that diazepam modifies the immune response of rats exposed to acute and chronic swim stress.