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In order to clarify the roles of platelet‐activating factor (PAF) in histamine‐ and thrombin‐induced neutrophil adhesion to vascular endothelial cells, the effects of several PAF antagonists were examined. The effects of the glucocorticoid dexamethasone were also examined in order to gain further insight into the anti‐inflammatory actions of glucocorticoids. In culture, histamine and thrombin stimulated the adherence of rat peritoneal neutrophils to human endothelial cells from the umbilical vein. They did not stimulate neutrophil adherence in the absence of endothelial cells, suggesting that the target cells for the histamine‐ and thrombin‐induced adherence of neutrophils were endothelial cells, not neutrophils. Several PAF antagonists, such as CV‐3988, L‐652,731 and Y‐24,180 inhibited the histamine‐ and thrombin‐induced neutrophil adherence in a concentration‐dependent manner. Indomethacin failed to inhibit it. Dexamethasone, a steroidal anti‐inflammatory drug, did not inhibit the histamine‐ and thrombin‐induced adherence of neutrophils to endothelial cells when the drug was present only during the 20 min incubation period for the adherence assay. When the endothelial cells were preincubated for 3 h with dexamethasone, the adherence of neutrophils to endothelial cells induced by histamine or thrombin was not inhibited. When the neutrophils were preincubated for 3 h with dexamethasone, the histamine‐ and thrombin‐induced adherence of neutrophils to endothelial cells was inhibited. Our studies indicate that: (a) adherence of neutrophils to endothelial cells induced by histamine and thrombin is mediated by PAF production since PAF antagonists inhibited the adherence of neutrophils; and (b) neutrophils, not endothelial cells, are the target cells through which dexamethasone acts to inhibit adherence.

The bronchodilating effect of magnesium sulfate (MgSO4) was studied in ten asthmatic patients with mild attacks. In five patients, 0.5 mmol/min of MgSO4 was administered intravenously for 20 minutes, and the time courses of respiratory resistance, forced vital capacity, and forced expiratory volume at 1 s were studied. In another five patients, MgSO4 dose-response curves were obtained. Soon after administration began, MgSO4 relieved bronchoconstriction in a dose-dependent manner. Maximum responses (mean +/- SE) of respiratory resistance, forced vital capacity, and forced expiratory volume were 71% +/- 3%, 117% +/- 5%, and 118% +/- 1% of initial values, respectively, and were similar to the effects of additional albuterol inhalation. The infusion of MgSO4 also improved dyspnea and piping rales in three other asthmatic patients with a severe attack. We conclude that intravenous infusion of MgSO4 produces a rapid and marked bronchodilation in both mild and severe asthma and may be a unique bronchodilating agent.

The role of histamine in neutrophil infiltration and vascular permeability response in carrageenin air pouch inflammation in rats was examined. Injection of carrageenin solution into an air pouch induced a gradual increase in histamine content in the pouch fluid and histidine decarboxylase activity of pouch wall tissues, with a maximum attained at 24 h. Local administration of the H2 antagonists cimetidine and famotidine, but not the H1 antagonist pyrilamine, induced an increase in neutrophil infiltration at 24 h. Both types of histamine antagonists failed to suppress the vascular permeability response. In addition, H2 antagonists attenuated the inhibitory effect of indomethacin on neutrophil infiltration without affecting the indomethacin-induced suppression of vascular permeability response. These results suggest that histamine produced in the inflammatory locus exerts a downward regulation of neutrophil infiltration through H2 receptors but does not play any significant role in the vascular permeability response. Furthermore, the inhibition by indomethacin of neutrophil infiltration might be ascribed to the increase in histamine level in the pouch fluid.

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