Prostaglandins and Medicine 7: 195-198, 1981 SUPPRESSION OF HUMAN POLYMCRPHONUCLEAR FUNCTION AFTER INTRAVENOUS INFUSION OF PROSTAGLANDIN El

نویسندگان

  • Joseph C. Fantone
  • Steven L. Kunkel
  • Peter A. Ward
چکیده

In two of three patients with peripheral vascular disease, systemic infusion of PGEl inhibited chemotactic factor induced secretion of glucosaminidase from neutrophils. Abundant experimental evidence now supports a view that prostaglandins of the E series can help regulate inflammatory responses. Although PGs appear to be local mediators of inflammation, (reviewed, 1) systemic administration of PGEl, methyl-PGE inflammation E2 and the stable El analog, 15-(S)-15!! suppress in several experimental animal models (2, ,4,5). In vitro studies suggest that the ability of these compounds to limit inflammation may result from inhibition of polymorphonuclear leukocyte (PMN) functions such as aggregation (6), enzyme release (7), and directed migration (chemotaxis) (8). In this report we describe neutrophil function in 3 patients who received systemic treatment with PGEl for peripheral vascular disease. Two of the patients exhibited significant inhibition of leukocyte function following PGEl treatment. This represents one of the first observations in humans of altered neutrophil function after in vivo treatment with PGEl. Three patients with peripheral vascular disease were treated with intravenous (I.V.) administration of PGEl (kindly provided by Dr. William Martin, Upjohn Co., Kalamazoo, Michigan). Each patient had peripheral total white blood cell counts and white blood cell differential counts within normal ranges. The patients received PGEl by continuous I.V. infusion of 3pg/hr for 6 hours followed by a 6 hours "rest" period and a second 6 hour infusion period. Peripheral blood neutrophils were isolated by Ficol gradient separation from three patients before PGEl treatment and 4 hours after the second 6 hour PGEl infusion period began. Secretion of the lysosomal enzyme N-acetyl-b-D-6glucosaminidase from cytochalasin B (Sng/ml) treated neutrophils (5x10 ) stimulated with N-formyl-methionylleucyl-phenylalanine (F-met-leu-phe) was determined (9). A range of F-met-leu-phe concentration was examined. This was compared to a similar dose response as determined in a healthy control individual. The Supported in part by NIH grants HL-23192 and AM-17309

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تاریخ انتشار 2003