Based on its involvement in eosinophil biology, interleukin 5 (IL-5) may play a role in the pulmonary eosinophilia associated with allergic reactions. We have examined that hypothesis using a neutralizing antibody to IL-5 in ovalbumin-sensitized guinea pigs challenged with aerosolized antigen. The extent of eosinophilia has been quantitated in bronchoalveolar lavage (BAL) and by histologic evaluation of lung tissue sections. Acute intraperitoneal administration of a rat IgG, monoclonal antibody to murine IL-5 derived from TRFK-5 cells prevented lung and BAL eosinophilia in a dose-dependent fashion at and above 10 micrograms per guinea pig. Treatment with either an experimentally irrelevant, isotype-matched antibody from GL113 cells or with heat-denatured IL-5 antibody was without effect. These studies demonstrate the importance of IL-5 to pulmonary eosinophilia in challenged, allergic guinea pigs.

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After the oral, intraperitoneal, or intravenous administration of an antihypertensive, antidiuretic benzothiadiazine, diazoxide, to dogs, rabbits, mice, and rats, rapid hyperglycemia is promptly elicited, but of short duration, and reversible. The hyperglycemia is accompanied by increased hepatic glycogenolysis, serum lactate and pyruvate, and blood urea nitrogen (BUN). The hyperglycemia is obtained in depancreatized dogs, alloxanized mice, propylthiouracil treated mice, and nephrectomized mice, suggesting that the pancreas, thyroid and kidneys are not the primary locus of action of diazoxide. Modification of diazoxide hyperglycemia by hypophysectomy suggests that the pituitary plays a role in the hyperglycemic phenomenon. However, this view must be tempered by the realization that hypophysectomy causes partial inanition, perhaps sufficient to prevent hyperglycemia. The partial suppression of diazoxide hyperglycemia by adrenalectomy and BW 61–43 (isopropyl methoxamine), a specific inhibitor of the metabolic effects of epinephrine, suggests that the metabolic effects of diazoxide are mediated, at least in part, by adrenergic hormones. Preliminary experiments wherein diazoxide hyperglycemia was markedly attenuated in adrenalectomized mice treated with a ganglionic blocking agent, chlorisondamine, tend to support this concept. However, some doubt is cast upon this concept since reserpine treated mice respond to diazoxide and differences were observed in the hyperglycemic responses to epinephrine and diazoxide in hypophysectomized mice. Further work is underway to elucidate the mechanism(s) and locus of action of the metabolic effects of diazoxide.

Loratadine is a new non-sedating antihistamine. The present studies compared loratadine and terfenadine, another non-sedating antihistamine, for their ability to inhibit the bronchial response to histamine and other autacoids which have been implicated as contributing to the symptoms of an allergic reaction. In addition, the two antihistamines were evaluated in models of immunologically mediated allergic reactions. Loratadine is a more potent inhibitor of histamine-induced bronchospasm in guinea pigs than is terfenadine. Both antihistamines exhibit marked antiserotonin activity at doses 10 times their antihistamine ED50 values. In contrast, loratadine and terfenadine produce little or no inhibition of the bronchial responses to methacholine, leukotriene C4 or platelet-activating factor. An allergic bronchospasm in guinea pigs is inhibited by loratadine (ED50 = 0.40 mg/kg, p.o.) and terfenadine (ED50 = 1.7 mg/kg, p.o.). The bronchospasm associated with allergic anaphylaxis in rats is significantly inhibited by 10 mg/kg, p.o. loratadine and 30 mg/kg, p.o. terfenadine. Loratadine exhibits antiallergy activity in vitro. At micromolar concentrations, loratadine inhibits the release of histamine from Con A and A23187-stimulated rat peritoneal mast cells and the release of histamine and leukotriene C4 from a Con A-stimulated cloned murine mast cell line.

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