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To evaluate the levels of leukotrienes (LTs), interleukin-2 (IL-2), interleukin-4 (IL-4), interferon-gamma (IFN-gamma) in patients with eczema and observe the effects inversed by mizolastine. Serum LTB4, LTC4, IL-2, IL-4, IFN-gamma and urinary LTE4 levels were detected by enzyme-linked immunosorbent assay (ELISA) and LTB4, LTC4, LTE4 concentrations of cutis tissue were measured by reverse-phase high-pressure liquid chromatography (RP-HPLC) in 10 eczema patients and 10 healthy volunteers. Eczema patients received mizolastine 10 mg once a day for 5 days, respectively, for comparison between before and after treatment. The above markers were assayed again after treatment. Serum LTB4, LTC4, IL-2, IFN-gamma and urinary LTE4 and skin tissue LTB4, LTC4, LTE4 levels in patients are higher than those in healthy volunteers significantly (P < 0.05). But serum IL-4 level did not show significant difference between patients and normal controls (P > 0.05). Mizolastine significantly reduced serum LTB4 and IFN-gamma levels as well as skin lesion LTB4, LTC4, LTE4 concentrations. LTs are involved in the pathogenesis of eczema. Mizolastine clearly reduces LTs levels in skin lesion.

Ibuprofen, a cyclooxygenase inhibitor, improves pulmonary and cardiovascular injury in endotoxemia. We studied the mechanism of the beneficial effects of ibuprofen in relation to production of inflammatory mediators which influence vascular tone in endotoxemia. Rats were randomly assigned to one of three groups: (1) control, (2) endotoxemia alone; and (3) ibuprofen pretreatment and endotoxemia. Plasma and lung lavage concentrations of tumor necrosis factor, thromboxane B2 (TXB2), leukotriene (LT) C4,D4,E4 and nitric oxide (NO) were determined over a 2 h period. Pretreatment with ibuprofen resulted in increased survival, and attenuation of pulmonary and cardiovascular dysfunction when compared to the rats receiving endotoxin alone. The marked elevation in plasma TXB2 concentration in endotoxemic rats was prevented by pretreatment with ibuprofen. Similarly, pretreatment with ibuprofen prevented the decrease in lung lavage NO levels in endotoxemic rats. The improved survival and cardiopulmonary protection in endotoxemic rats pretreated with ibuprofen appears to be related to decreased thromboxane production and preservation of endothelial production of nitric oxide.

Leukotrienes (LTs) are biologically active compounds derived from lipoxygenase catalyzed metabolism of arachidonic acid in mammalian tissues. The present report describes a simple method for extraction and isolation of dihydroxy-LTs; LTB4, LTB5 and the peptido-LTs; LTC4, LTD4 and LTE4 from human plasma, using a pretreatment cartridge which utilizes both hydrophobic and ion-exchange interactions. 5 ml acidified plasma or acetate buffer containing commercially available LT standards were passed through the cartridges under suction, and the absorbed LTs were subsequently eluted in a stepwise manner with acetate buffer containing increasing amounts of methanol. The eluted LTs were analyzed by reversed-phase high performance liquid chromatography (HPLC) on octadecylsilyl (ODS)-silica, using a Waters HPLC unit. Both with plasma and acetate buffer the present methodology resulted in good separation of the LTs with a total run-time of less than 32 min. Recovery of dihydroxy-LTs was approximately 80% (range 73-82%) both when the standards were dissolved in plasma and in acetate buffer. Recovery of the peptido-LTs was, however somewhat lower (47-50%). It should be noted that the present method has the advantage that exposure to chemicals of high toxicity is avoided.

Fish oil was fed to rats in combination with an equal amount of olive, sunflower or linseed (flax) oil in semisynthetic diets for 3 weeks. Following stimulation of isolated neutrophils with calcium ionophore the levels of leukotrienes (LT) were determined by HPLC. Graphical presentation of the resultant data show a direct linear relationship between LTB production and substrate concentration with no preferential conversion of n-3 or n-6 substrates. In addition the results highlighted the greater conversion of eicosapentaenoic acid (EPA) and arachidonic acid (AA) to 5-hydroxy metabolites in stimulated neutrophils. There is no suggestion in our results of inhibition of any of the enzymatic conversion steps between EPA or AA and LTB production by any of the dietary fatty acids except by altering the EPA/AA ratio in neutrophil membranes.

Recently identified Ascaris suum sensitive cynomolgus monkeys were further characterized to determine if a chronologic relationship existed between mediator release and onset of bronchoconstriction. In these anesthetized Ascaris-sensitive monkeys, aerosol antigen challenge of each animal produced rapid and severe bronchoconstriction, as determined by decreases in dynamic lung compliance (-80.2 +/- 4.1%) and airway conductance (-64.5 +/- 13.8%). Maximum changes were achieved within 5 min following exposure and remained substantially altered throughout the 30 min observation period. However, changes in pulmonary function related to duration of onset and maximum change seemed to have some correlation with each animals' sensitivity to the antigen. Comparison of pre- and post-challenge blood gas profiles, showed a progressive formation of respiratory acidosis through decreases in arterial blood pH, partial pressure of O2 (pO2), O2 saturation (sO2) and an increase in partial pressure of CO2 (pCO2). When arterial blood plasma was assayed by RIA for mediators of anaphylaxis, large increases in 5-hydroxyeicostetraenoi acid (5-HETE), leukotriene B4 (LTB4) and histamine were observed. No amount of prostaglandin F2-alpha (PGF2 alpha) or thromboxane A2 were detected. Two of the three monkeys also produced detectable amounts of leukotriene C4 (LTC4). Therefore, in Ascaris-sensitive monkeys, histamine is the predominate mediator released and is probably responsible for at least the early part (5-10 min) of the observed bronchoconstriction. However, mediators from the lipoxygenase pathway may also be playing a role in the antigen-induced bronchoconstriction, especially beyond the 10 min period following anaphylaxis.