The effect of heat-inactivated Helicobacter pylori on the blastogenic response of peripheral blood mononuclear cells of patients with chronic urticaria.

BACKGROUND: Helicobacter pylori, the most important etiologic factor of gastritis and peptic ulcer, has recently been associated with several extradigestive diseases. Previous studies reported conflicting results on H. pylori eradication in chronic urticaria, in that some studies showed a benefit, while others found no effect. METHODS: Peripheral blood mononuclear cells of 24 chronic urticaria patients (13 seropositive/11 seronegative for H. pylori) and 18 healthy controls (9 seropositive/9 seronegative) were stimulated with whole heat-inactivated H. pylori (8 x 10(5), 8 x 10(6 )and 8 x 10(7) bacteria/well), phytohemagglutinin (2 microg/ml) and pokeweed mitogen (5 microg/ml). The proliferative response was determined by (3)H-thymidine incorporation. Helicobacter-specific IgG antibody response was determined by ELISA. RESULTS: There were significantly higher proliferative responses to various concentrations of whole heat-inactivated H. pylori antigen in 6- to 7-day cultures of peripheral blood mononuclear cells of chronic urticaria patients compared to healthy controls. We found a tendency to exhibit a higher proliferative response to either Helicobacter antigens or mitogens in seropositive compared to seronegative patients. CONCLUSION: Our results support the hypothesis that there is an increased lymphocyte reactivity in chronic urticaria, perhaps further enhanced by the presence of H. pylori which, therefore, may be involved as a trigger in the pathogenesis of chronic urticaria.

Effect of silibinin and vitamin E on restoration of cellular immune response after partial hepatectomy.

Our aim was to study the antioxidant and immunomodulatory effect of silibinin and vitamin E on the early postoperative course in rats that had undergone a partial hepatectomy (PHX). Male Wistar rats that were treated with silibinin (50 mg/b.w.kg i.p.) and/or vitamin E (500 mg/b.w.kg p.o.) were randomised to undergo 70% PHX. At 72 h after operation, Concanavalin A (Con-A) induced lymphocyte proliferation, and lipopolysaccharide (LPS) induced interleukin-1 (IL-1) mitogenicity and tumour necrosis factor-alpha (TNF-alpha) cytotoxicity were measured in the spleen. In addition, total free radical scavenger capacity of the liver was analysed. In PHX animals, Con-A induced lymphocyte proliferation was significantly decreased, and both LPS induced IL-1 and TNF-alpha activity were significantly increased as compared to Sham treated animals. Treatment with silibinin and vitamin E synergistically restored both lymphocyte proliferation (P<0.01) and cytokine activity (P<0.001) in PHX animals. In addition, silibinin and vitamin E synergistically (P<0.001) restored total hepatic free radical scavenger capacity as well as serum levels of AST and gammaGT, that were all markedly decreased in PHX animals. Our results suggest that preoperative treatment with silibinin and/or vitamin E modulates the cellular immunoresponse and restores impaired liver function following PHX, presumably through their antioxidant capacity. This may explain their beneficial effects on the postoperative course of liver repair.

Effects of boldine on cellular immune functions in vitro.

The in vitro effects of boldine on natural killer (NK) cells, lectin-dependent cell-mediated cytotoxicity (LDCC) and lectin-induced blast transformation were studied in patients with breast cancer, chronic lymphocytic leukemia (CLL) and healthy donors. NK activity was measured against [51Cr]-labeled K-562 targets cells. LDCC and natural cell-mediated cytotoxicity (NCMC) were assessed using [3H]-thymidine-prelabeled HEp-2 cells. Lectin (PHA and Con A)-induced blast transformation was measured by thymidine incorporation. Boldine concentration-dependently decreased blastogenesis in normal subjects and patients with CLL. However, the decrease in breast cancer patients was significant only at higher concentrations. NK activity showed no change in healthy controls with normal values, but in cases with low activity treatment with boldine resulted in an increase. In patients with CLL, NK activity was enhanced; in tumor-bearing patients, however, there was no effect. LDCC and NCMC activity did not change significantly in normal controls. In patients with CLL, NCMC activity significantly increased. In tumor-bearing patients, LDCC activity was strongly enhanced by higher concentrations of boldine, whereas NCMC activity changed significantly only at the concentration of 1.0 microgram/ml.

Effect of vitamin E on the immunoreactivity of spleen cells in hyperlipidaemic rats.

Atherogenic (lipid-rich) diet suppressed mitogen-induced lymphocyte blastogenic responses in rats. Supplementation with vitamin E completely abolished the suppressive effect of the diet. The atherogenic diet also decreased the tumour necrosis factor alpha (TNF-alpha) activity produced by spleen macrophages, however, vitamin E supplementation failed to abolish this effect. Diet or supplementation had no measurable action on interleukin-1 (IL-1) production of macrophages.

[Cytokine production in patients with systemic lupus erythematosus]. / Systemás lupus erythematosusban szenvedö betegek cytokin termelésének vizsgálata.

The production of different cytokines, namely interleukin-2, interleukin-1 and tumor necrosis factor-alpha produced by peripheral immunocompetent cells was evaluated in patients with systemic lupus erythematosus in active and inactive stage of the disease. The results obtained were compared to healthy controls. It has been found that lymphocytes from both groups of SLE patients produced similarly less interleukin-2 activity. Interleukin-1 activity of monocytes was significantly reduced only in patients with active stage of the disease, whereas tumor necrosis factor-alpha production was diminished even in cases of inactive SLE. The simultaneous detection of the above mentioned cytokines may indicate further details concerning immunoregulatory disturbances of systemic lupus erythematosus.

[Immunomodulator effect of silymarin therapy in chronic alcoholic liver diseases]. / Silymarin kezelés immunmoduláns hatása krónikus alkoholos májbetegségben.

The effects of the hepatoprotective, antioxidant drug silymarin (Legalon) on some cellular immune parameters of patients with histologically proven chronic alcoholic liver disease were studied in a six month double blind study. The lectin induced proliferative activity of the lymphocytes got enhanced, the originally low T cell percentage and the originally high CD8+ cell percentage have been normalized, the antibody-dependent and natural cytotoxicity of the lymphocytes decreased during silymarin therapy. All these changes were significant, while in the placebo group no significant changes occurred, except for a moderate elevation of the T cell percentage. Thus, the immunomodulatory activity of silymarin might be involved in the hepatoprotective action of the drug and improves the depressed immunoreactivity of the patients.

Hepatoprotective and immunological effects of antioxidant drugs.

The hepatoprotective and immunomodulatory effects of silymarin and amino-imidazole-carboxamide-phosphate were studied in 40 patients with alcoholic cirrhosis of the liver in a one-month double-blind clinical trial. Treatment with either of the drugs normalized the elevated levels of aspartate aminotransferase, alanine aminotransferase and serum bilirubin, markedly reduced the high level of gamma-glutamyl transferase, increased lectin-induced lymphoblast transformation, decreased the percentage of OKT8+ cells and suppressed lymphocytotoxicity. None of these changes occurred in the placebo-treated group. Thus, the hepatoprotective effects of silymarin and amino-imidazole-carboxamide-phosphate in alcoholic cirrhosis can partly be attributed to the immunomodulatory activity of the drugs.

Effect of in vitro Aica-P treatment on certain cellular immune functions.

The effect of the hepatoprotective agent and protein synthesis stimulator 4-amino-5-imidazole-carboxamide-phosphate on the resynthesis of the "E" receptors of T lymphocytes and on certain immunological functions was investigated in vitro. Aica-P treatment enhanced the resynthesis of the "E" receptors after trypsin digestion and inhibited the blastic transformation of the lymphocytes. The results corroborate the observations that Aica-P is able to enhance protein synthesis and to exert immunomodulatory activity.

Effects of two bioflavonoids on certain cellular immune reactions in vitro.

Oxidative and autoaggressive immune processes are supposed to be involved in the pathogenesis of certain chronic liver diseases. In this study the effects of two naturally occurring antioxidant flavonoids, (+)cyanidanol-3 and silymarin, were determined on T and active T cell percentages, antigen-dependent (ADCC), lectin-dependent (LDCC) and natural (NK) cell mediated cytotoxicity and on lectin induced blast transformation of lymphocytes from healthy subjects and patients with chronic alcoholic liver disease in vitro. We observed no effects on T and active T cell percentages and on ADCC activity. Both drugs decreased LDCC activities of patients and lectin-induced lymphoblast transformation of controls and patients, (+)cyanidanol slightly and silymarin significantly decreased NK activities of controls and patients. These suppressive effects could partly be explained by the free radical scavenger and lipoxigenase inhibitor activity of the drugs and support the promising role of bioflavonoids in the treatment of chronic liver diseases.

Cyclic AMP level of lymphocytes in patients with systemic lupus erythematosus and its relation to disease activity.

The basal and stimulated intracellular cyclic AMP (cAMP) levels of peripheral blood mononuclear cells (PBMC) of 16 control subjects and 14 patients with systemic lupus erythematosus (SLE), all fulfilling the ARA criteria, were studied. No significant difference in basal cAMP level was observed between SLE patients and controls. SLE lymphocytes (both active and inactive) elicited a diminished response to aminophylline and prostaglandin E2 (PGE2). No correlation was seen between disease activity and either baseline cAMP levels or response to these stimulators. We suggest an intrinsic (not disease activity-related) impairment of the adenylate cyclase-dependent regulatory mechanism in the PBMC of SLE patients, which may result in a defective IL-2 production and IL-2 dependent biological functions.

Depressed monocyte production of interleukin-1 and tumor necrosis factor-alpha in patients with alcoholic liver cirrhosis.

Interleukin-1 and tumor necrosis factor-alpha activity by E. coli lipopolysaccharide-triggered monocytes were studied in patients with chronic alcoholic liver disease. Monocytes from cirrhotic patients were shown to have a significant reduction in IL-1 and TNF-a activity, compared with that from age- and sex-matched healthy controls. These findings indicate further immunoregulatory disturbances concerning alcoholic liver cirrhosis.

A simple assay for tumor necrosis factor using HEp-2 target cells.

We developed a sensitive bioassay system for the determination of tumor necrosis factor-alpha (TNF) using HEp-2 adherent human epipharynx carcinoma cells as targets. TNF from separated human monocytes was triggered by lipopolysaccharide (LPS). In a 24 hr 3H-thymidine incorporation assay, TNF-like activity was seen to reproducibly destroy radiolabeled target cells, i.e., inhibits thymidine incorporation and causes detachment of adherent HEp-2 cells. HEp-2 cells were insensitive to human interleukin-1 (IL-1) and interleukin-2 (IL-2). In contrast, human interferon-alpha and gamma were also cytotoxic for target cells. Monocyte supernatants stimulated by LPS, however, failed to contain detectable amounts of interferons.

Defective production of interleukin-1 and tumour necrosis factor-alpha by stimulated monocytes from patients with systemic lupus erythematosus.

Interleukin-1 and tumour necrosis factor-alpha activity by E. coli lipopolysaccharide-triggered monocytes was studied in patients with systemic lupus erythematosus in various stages of activity. Monocytes from both groups of SLE patients produced significantly less tumour necrosis factor-alpha activity than those of age and sex matched healthy controls. However, interleukin-1 activity was only significantly reduced in patients with active stage of the disease. These findings indicate further immunoregulatory disturbances in monocyte function concerning SLE.

Studies on the monocyte interleukin-1 and tumour necrosis factor-alpha production in patients with alcoholic liver cirrhosis.

Interleukin-1 and tumour necrosis factor-alpha activities by E. coli lipopolysaccharide-triggered monocytes were studied in patients with chronic alcoholic liver disease. Monocytes from cirrhotic patients were shown to have significantly reduced IL-1 and TNF-a activities, compared with that from age and sex matched healthy controls. These findings indicate further immunoregulatory disturbances concerning alcoholic liver cirrhosis.

Effect of vitamin A treatment on immune reactivity and lipid peroxidation in patients with Sjögren's syndrome.

Patients with Sjögren's syndrome were treated with vitamin A (100,000 U) daily during a two-week period. The vitamin treatment significantly elevated their ADCC and NK activity. The lymphocyte blast transformation, however was not noticeably changed. After the treatment, the retinyl-ester and retinol level of the plasma significantly increased as did the plasma level of vitamin E. The level of TBA reactive substances (malondialdehyde) in the plasma increased, whilst the glutathione peroxidase and catalase activity of erythrocytes decreased. The activity of the plasma glutathione peroxidase increased, but not significantly.

Effect of vitamin A treatment on the immune reactivity of patients with systemic lupus erythematosus.

Treatment of patients suffering from systemic lupus erythematosus with vitamin A (100,000 U daily for 2 weeks) resulted in an enhancement of antibody-dependent cell-mediated cytotoxicity, natural killer cell activity and blastogenic response to plant mitogens and interleukin-2 (IL-2).

Effect of vitamin A treatment on cellular immune reactivity in patients with CLL.

Treatment with vitamin A (100,000 U daily for 2 weeks) of patients suffering from chronic lymphocytic leukaemia resulted in an enhancement of antibody-dependent cell-mediated cytotoxicity, natural killer cell activity and blastogenic response to plant mitogens.

Hepatoprotective and immunomodulatory effects of antioxidant therapy.

The hepatoprotective and immunomodulatory effects of silymarin and amino-imidazole-carboxamide-phosphate were studied in 40 patients with alcoholic cirrhosis of the liver in a one-month double-blind clinical trial. Treatment with either of the drugs normalized the elevated levels of aspartate aminotransferase, alanine aminotransferase and serum bilirubin, markedly reduced the high level of gamma-glutamyl transferase, increased lectin-induced lymphoblast transformation, decreased the percentage of OKT8+ cells and suppressed lymphocytotoxicity. None of these changes occurred in the placebo-treated group. Thus, the hepatoprotective effects of silymarin and amino-imidazole-carboxamide-phosphate in alcoholic cirrhosis can partly be attributed to the immunomodulatory activity of the drugs.

[Effect of female sex hormones on blastic transformation of lymphocytes in systemic lupus erythematosus and in healthy women]. / A nöl nemi hormonok hatása a lymphocyta blastos transformatióra systhemás lupus erythematosusban és egészséges nökben.

PIP: The susceptibility of women to autoimmune diseases is well-documented, of which systemic lupus erythematosus (SLE) is especially important. The use of oral contraceptives often activate SLE from a quiescent condition. The inductive effect of estrogen has been shown in animal studies indicating that female hormones can trigger autoimmune reaction. The effect of ethinyl estradiol, an estrogen (E), and d-norgestrel, a progesterone (P), on the mitogenic response of peripheral lymphocytes, and particularly on phytohemagglutinin (PHA)- and concanavalin-A (Con-A)-induced blastic transformation of lymphocytes (LBT) was studied in vitro. 25 patients with SLE and 27 healthy controls participated in the study. SLE was inactive in 16 patients, 7 took corticosteroids, and 3 also received 50 mg/day Imuran. 13 patients and 10 controls took contraceptives (Bisecurin, Infecundin, Ovidon, Rigevidon). The LBT value fell significantly in patients with active SLE, in contraceptive users, and the value was significantly lower in inactive patients than in those not using contraceptives. E and P separately or together significantly reduced LBT values. Contraceptives containing P only can be prescribed for women suffering from SLE, as its role in inducing the disease compared to E is negligible.^ieng

[Effect of hyperlipemia on mitogen-induced blastogenesis in lymphocytes isolated from the rat spleen]. / Efecto de la hiperlipemia sobre la blastogénesis inducida por mitógenos, en linfocitos aislados de bazos de ratón.

Lipoproteins suppress several immune functions (mitogen-induced lymphoblast transformation, macrophage functions). Low density lipoprotein (LDL) is responsible for most of these effects. Diet may cause an elevation in LDL level. Therefore, we investigated the effect of cholesterol-rich diet upon the mitogen response of rats. The cholesterol and LDL-cholesterol level of rats was elevated after 8 days of diet. The blastogenic response of spleen cells separated by Ficoll-Paque gradient decreased. The response to phytomitogens 1, and 10 micrograms/ml phytohaemagglutinin (PHA) and 10 micrograms/ml concanavalin A (Con A) was measured by thymidine incorporation after 3 days of culture. The decrease of blastogenic response was more pronounced at the higher doses (10 micrograms/ml PHA, and 10 micrograms/ml Con A). For the lymphocyte cultures that did not contain autologous (rat) serum, we suggest that suppressed response was caused by an alteration of either in the membrane or in the metabolism of cells participating in the mitogen response. The decreased amount of LDL receptors and a derangement in intracellular cholesterol biosynthesis are supposed. The clinical implications of the immunosuppressive effect of dietary cholesterol is discussed.