leukotriene-b4 and Multiple-Sclerosis

Topics: Adult; Aged; Aging; Alcoholism; Amino Acids; Anesthetics, Local; Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Aqueous Humor; Autonomic Nervous System; Biological Transport, Active; Brain Chemistry; Cardiac Glycosides; Catecholamines; Cell Differentiation; Central Nervous System; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Epidermal Growth Factor; Eye; Fibrinolysis; Glaucoma; Granuloma; Graves Disease; Hallucinogens; Humans; Hypertension; Immunity, Cellular; Infant; Infant, Newborn; Leukotriene B4; Metabolism, Inborn Errors; Multiple Sclerosis; Muscle Relaxation; Nutritional Physiological Phenomena; Oxygen; Oxygen Consumption; Pigment Epithelium of Eye; Pineal Gland; Prostaglandin Antagonists; Prostaglandins; Psychotropic Drugs; Retina; Retinal Degeneration; Serotonin; Smoking; SRS-A; Stress, Physiological; Water-Electrolyte Balance

Leukotrienes B4 and C4 have been assayed in CSF of 24 patients with the attacks or slowing-progressing course of multiple sclerosis, and in 23 patients with other noninflammatory diseases. Leukotrienes concentrations have been assayed with RIA technique with the use of commercially available kits manufactured by Amersham. Leukotrienes B4 and C4 levels in CSF of patients with multiple sclerosis have been 91.8 +/- 5.6, and 88.6 +/- 7.5 pg, and have been significantly higher than those in other neurological disorders (p < 0.01). Mean LTB4 and LTC4 levels have been significantly lower in patients with atherosclerotic dementia (69, 12.2 and 63, 02.9 pg/ml) or in patients with headache (72.7 +/- 2.8 and 64.5 +/- 8.2 pg/ml). Higher LTB4 and LTC4 levels in patients with multiple sclerosis is probably due to both increased penetration through blood-brain barrier and their synthesis in blood-brain barrier, and cerebral nervous tissue. Further investigations are necessary to show whether LTB4 and LTC4 levels may indicate a stage of inflammatory process activity and enable to draw any conclusions on efficacy of anti-inflammatory therapy.

Topics: Blood-Brain Barrier; Humans; Leukotriene B4; Leukotriene C4; Multiple Sclerosis; Radioimmunoassay

The role of leukotrienes (LTs) in the pathophysiology of multiple sclerosis (MS) has been controversially discussed in the past. Studies of LTs in the cerebrospinal fluid (CSF) revealed different results mainly because of analytical difficulties.. In the present study we used highly sensitive and specific analytical methods for measuring LTs in the CSF as well as in urine samples from 20 patients with active MS and 20 control patients with noninflammatory neurological disorders.. LTB4 concentrations in CSF were almost twice as high in MS patients compared with controls (P < 0.001). CSF concentrations of the cysteinyl-LTs (LTC4, LTD4 and LTE4) as well as urinary LTE4 showed no significant differences compared with controls (P > 0.05). In addition, there was no significant association between CSF pleocytosis, clinical severity or time of disease onset.. The increased concentration of LTB4 in the CSF of MS patients may indicate a biological importance for this mediator in MS.

Topics: Adolescent; Adult; Age Factors; Aged; Female; Humans; Leukotriene B4; Leukotriene C4; Leukotriene D4; Leukotriene E4; Male; Middle Aged; Multiple Sclerosis; Severity of Illness Index

To demonstrate the influence of n-3 PUFA supplementation on cytokine and eicosanoid production in peripheral blood mononuclear cells (PBMCs) of MS patients (MSP), we investigated the impact of a 6-month dietary supplementation with these fatty acids on the levels of interleukin-1 beta (IL-1 beta), IL-2, interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) in the supernatants of stimulated PBMCs and serum soluble IL-2 receptors in a group of 20 relapsing-remitting (R-R) MSP and a group of 15 age-matched control individuals (CI). The production of PGE2 and LTB4 in the stimulated PBMCs was also assessed in patient and control groups supplemented with n-3 PUFAs. In both groups, n-3 PUFA supplementation led to a significant decrease in the levels of IL-1 beta and TNF-alpha, and this reduction was more pronounced in the 3rd and 6th month of supplementation. An analogous decrease was observed in the levels of IL-2 and IFN-gamma produced by stimulated PBMCs, and in the levels of serum soluble IL-2 receptors. n-3 PUFA supplementation also appeared to significantly affect prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) production in PBMCs, both in MSP and the control group. The reduced production of these proinflammatory eicosanoids, and the decrease of some cytokines with an immunohenancing effect as a consequence of n-3 PUFA supplementation, could modulate some immune functions which have been demonstrated to be altered in MSP.

Topics: Adult; Cytokines; Dinoprostone; Fatty Acids, Omega-3; Humans; Interferon-gamma; Interleukin-1; Interleukin-2; Leukocytes, Mononuclear; Leukotriene B4; Lipopolysaccharides; Middle Aged; Multiple Sclerosis; Receptors, Interleukin-2; Tumor Necrosis Factor-alpha

The in vitro effect of methylprednisolone on prostaglandin E2 (PGE2), leukotriene B4 (LTB4) and thromboxane B2 (TXB2) synthesis by adherent monocytes was examined using samples of peripheral blood from 15 patients with multiple sclerosis and 18 normal controls. Eicosanoid production by monocytes was reduced in patients compared with controls and there was a dose-dependent inhibitory effect of methylprednisolone on eicosanoid production in both groups. In vitro production of PGE2 and TXB2 but not LTB4 was reduced in patients with multiple sclerosis following intravenous treatment with methylprednisolone compared with pretreatment samples. In a separate cohort of 20 patients with multiple sclerosis and 15 controls, the in vitro inhibition of PGE2 release by methylprednisolone was not associated with reduced pokeweed-mitogen-stimulated immunoglobulin G synthesis by peripheral blood mononuclear cells. These results suggest that methylprednisolone inhibits monocyte-macrophage function, but this effect is not specific to patients with multiple sclerosis.

Topics: Adult; Cells, Cultured; Dinoprostone; Dose-Response Relationship, Immunologic; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoglobulin G; Leukotriene B4; Male; Methylprednisolone; Monocytes; Multiple Sclerosis; Pokeweed Mitogens; Radioimmunoassay; Thromboxane B2

The concentration of the leukotrienes B4 (LTB4) and C4 (LTC4) was measured in the cerebrospinal fluid (CSF) of 38 multiple sclerosis (MS) patients and 51 with other neurological diseases. The LTB4 and LTC4 levels were significantly elevated in MS compared with the controls. The findings suggest that lipoxygenase products might play a pathogenetic role in the early, encephalitogenic phase of MS. The administration of lipoxygenase inhibitors or leukotriene antagonists might well open new perspectives for the treatment of MS.

Topics: Adult; Female; Humans; Leukotriene B4; Male; Middle Aged; Multiple Sclerosis; Neurologic Examination; SRS-A

Prostaglandin E levels have previously been demonstrated to be elevated in multiple sclerosis (MS). We have further investigated other products of activated macrophages related to inflammation. We report here on prostaglandin E and its relationship to interleukin 1, tumor necrosis factor, and leukotriene B4 produced by macrophages from blood and cerebrospinal fluid of MS patients and controls in vitro. Interleukin and tumor necrosis factor are elevated significantly after stimulation in MS, while leukotriene B4 production by blood macrophages is depressed compared to other neurological disease and normal healthy controls. In 40% of MS patients tested, peripheral blood macrophages spontaneously produced elevated levels of interleukin 1. All mediators of inflammation are produced in increased amounts by MS cerebrospinal fluid leukocytes after stimulation. Macrophages from MS blood are not as sensitive as controls to nonsteroidal inhibitors specific for lipoxygenase or cyclo-oxygenase pathways. Positive correlations of elevations in production of such mediators of inflammation as prostaglandin E, interleukin 1, and tumor necrosis factor in MS were significant. Elevated production of these mediators in combination with insensitivity to inhibitors of inflammation suggests a role for activated macrophages in the demyelination process.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cells, Cultured; Female; Humans; Inflammation; Interleukin-1; Leukotriene B4; Macrophages; Male; Multiple Sclerosis; Neuromuscular Diseases; Prostaglandins E; Tumor Necrosis Factor-alpha

The author assessed the effect of leucotrienes B4 and C4 and the calcium ionophore A23187 on the adherent reactivity of mononuclear leucocytes in patients with multiple cerebrospinal sclerosis and in controls. The calcium ionophore A23187 in concentrations of 200 nmol/1 - 5 mumol/1 induced inhibition of leucocyte adherence, depending on the concentration used. This reactivity was, as compared with controls, significantly lower in patients with multiple sclerosis who did not take cortisoid preparations and in patients taking prednisone in doses up to 5 mg/day. In patients treated with higher prednisone doses (20-90 mg/day) the values of the non-adherence index reached values insignificantly higher than in controls. Leukotrienes B4 and C4 (1 nmol/1 - 100 nmol/1 stimulated leucocyte adherence in patients treated with higher corticoid doses, in the remaining patients and in controls they did not influence the leukocyte adherence. The results of the investigation provide evidence of abnormalities of the membrane properties of the mononuclear leucocytes in patients with multiple sclerosis and draw attention to the association of these changes with metabolic chains of arachidonic acid and with calcium ion homeostasis.

Topics: Adult; Calcimycin; Female; Humans; Immunologic Techniques; Leukocyte Adherence Inhibition Test; Leukotriene B4; Male; Middle Aged; Multiple Sclerosis; SRS-A

The disturbances of the arachidonic acid metabolic cascade are supposed to play a significant part in some membrane alterations and in associated immunopathological changes in multiple sclerosis. Since the lipoxygenase derivatives of the arachidonic acid and the calcium ion influx were proved to participate in the mechanisms involved in the leucocyte adherence inhibition phenomenon, the effect of calcium ionophore A23187 and of leukotrienes B4 and C4 upon the adherence of mononuclear leucocytes of multiple sclerosis patients and of healthy controls was investigated in the present study using a modification of the leucocyte adherence inhibition assay. A23187, a potent stimulator of the arachidonic acid metabolism, induced the mononuclear leucocyte adherence inhibition in a dose-dependent manner. In multiple sclerosis patients without corticosteroid treatment and in those treated with lower prednison doses (up to 5 mg/day), the non-adherent response to A23187 stimulation was significantly lower than in the controls, whereas in multiple sclerosis patients treated with prednison doses varying from 20 to 90 mg/day the A23187-induced adherence inhibition reached non-significantly higher values compared to the controls. Leukotrienes B4 and C4 stimulated the adherence of the leucocytes in multiple sclerosis patients treated with higher prednison doses. Compared to controls, statistically significant differences were found using 1 nM and 100 nM LTC4. The findings obtained in this study with all probability reflect alterations of the membrane processes in multiple sclerosis leucocytes associated with calcium ion homeostasis and arachidonic acid metabolic cascade.

Topics: Adult; Calcimycin; Calcium; Female; Humans; Leukocyte Adherence Inhibition Test; Leukocytes, Mononuclear; Leukotriene B4; Male; Middle Aged; Multiple Sclerosis; SRS-A

Release of leukotriene B4 (LTB4) and leukotriene C4 (LTC4) from neutrophils and platelet-neutrophil suspensions in response to ionophore A23187 was measured in 12 multiple sclerosis (MS) patients and 8 healthy volunteers. LTC4 release from neutrophils, as well as from platelet-neutrophil suspensions, was significantly decreased in MS patients compared with the controls. There was no significant difference in the release of LTB4 between MS patients and controls. The findings suggest that permanent stimulation of platelets and neutrophils e.g., by encephalitogenic peptide leads to continuous LTC4 release with subsequent depletion of intracellular substrates serving as precursors for the formation of 5-lipoxygenase products. Since the target of microvascular actions of LTC4 are postcapillary venules, the release of this sulfidopeptide leukotriene might play a pathogenetic role in the formation of MS lesions.

Topics: Adult; Blood Platelets; Calcimycin; Female; Humans; Leukotriene B4; Male; Middle Aged; Multiple Sclerosis; Neutrophils; SRS-A