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Abstract

We have previously demonstrated that the detergent Tyloxapol is effective in preventing reactions to endotoxin. We studied the effects of Tyloxapol on the morbidity and mortality from endotoxemia in rabbits and on the mortality in rats with sepsis. The effects of Tyloxapol on endotoxin binding and macrophage activation were studied in the macrophage cell line RAW264.7 and CHO cells expressing CD14. Isolated human leukocytes were used to study the effects of Tyloxapol on immune reactions, leukocyte motility, and phagocytosis. Intravenous Tyloxapol (200 mg/kg), given prior to or at the time of endotoxin infusion protected rabbits from developing shock. In rats with peritoneal sepsis, a lipid-rich diet and Tyloxapol given at the time of induction of peritonitis protected them from septic death. In vitro, Tyloxapol blocked the binding of endotoxin to murine macrophages and CHO cells expressing CD14, activation of macrophages, and also some antigen-antibody immune reactions (mediated by CD2, CD4, CD22, HLA-DR). Tyloxapol may prevent the reaction to endotoxin by desensitizing endotoxin-recognizing receptors.

Interactions between U-937 human macrophages and tyloxapol

“…Tyloxapol attenuated the pathologic effects of endotoxin in vivo and in vitro [2,7] by desensitizing endotoxin-recognizing receptors in macrophages. Also, tyloxapol has functioned as antioxidant for hydroxyl radicals and hypochlorous acid in vitro and in vivo [9,15].…”

“…Tyloxapol (Triton WR-1339), an alkyl aryl polyether alcohol polymer, is a nonionic surfactant widely used in biomedical applications [1][2][3][4][5][6][7][8][9]. Due to its excellent properties as a surfactant, tyloxapol is a versatile and cost-effective ingredient in many commercial pharmaceutical products [1].…”

“…Tyloxapol is extensively used in, for example, contact-lens detergent [1], mucolytic agents for pulmonary diseases [1], inflammatory modulators for endotoxin-induced activations [2,[7][8][9], components for self-emulsifying drug-delivery systems and synthetic-lung surfactants [3,6], a model of hyperlipidemic atherogenesis [5], and a powerful upregulator of dendrimer-mediated transfection [4]. One attractive use for tyloxapol is as a prophylactic against endotoxins, such as lipopolysaccharide (LPS), which are believed to be a major factor in the systemic inflammatory response syndrome (SIRS) [2,[7][8][9]. Tyloxapol attenuates the pathologic effects of endotoxin in vivo and desensitizes endotoxin-recognizing receptors in macrophages [2].…”

“…One attractive use for tyloxapol is as a prophylactic against endotoxins, such as lipopolysaccharide (LPS), which are believed to be a major factor in the systemic inflammatory response syndrome (SIRS) [2,[7][8][9]. Tyloxapol attenuates the pathologic effects of endotoxin in vivo and desensitizes endotoxin-recognizing receptors in macrophages [2]. However, we previously showed that tyloxapol induces apoptosis in macrophages in vitro [10].…”