lactoferrin and Pruritus

Complement (C) activation, neutropenia, and mild pulmonary dysfunction attend hemodialysis (HD) with cellophane [for example, cuprophan (Cu)] membranes. While usually asymptomatic, these phenomena may cause distress in patients with cardiopulmonary disease, and "start-up" symptoms of HD might be mediated by C-stimulated granulocytes (PMNs). Cellulose acetate (CA) hemodialysis membranes have been devised and claimed more blood compatible than Cu. In a blinded series of HD patients, pruritus, fatigue, and sense of well-being were each scored statistically more favorably by the patients during HD with CA than during HD with Cu (P less than 0.05). Postulating that less C activation might underlie the benefit, we showed that neutropenia was less severe with CA (nadir 77.6% of initial count, +/- 4 SEM) than with Cu (38.3% +/- 2.9; P less than 0.01). In vitro, incubation of CA membranes with plasma led to less C3 conversion (20% vs. 40%), less PMN aggregating activity (5.9 ZAP units vs. 36.3) and less decrement in CH50 (6.5% vs. 22%) than like incubations of Cu. C activation was also less potent in vivo: During HD plasma C3a rose from a mean 401 ng/ml to a peak 6,325 in patients on Cu dialyzers, but from 426 to only 3,637 in patients on CA devices (P less than 0.05). Time-course studies suggested CA was initially as potent an activator as Cu but rapidly lost ability to activate C, possibly because of saturation of C3b binding sites. As an index of PMN activation, we also assayed plasma lactoferrin and found levels significantly higher during Cu than CA dialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anaphylatoxins; Biocompatible Materials; Cellulose; Complement Activation; Complement C3; Complement C3a; Complement C5; Complement C5a; Fatigue; Humans; Kidneys, Artificial; Lactoferrin; Lymphocyte Activation; Membranes, Artificial; Neutropenia; Neutrophils; Prospective Studies; Pruritus; Renal Dialysis; Time Factors

Ivermectin is a safe and effective drug for onchocerciasis treatment. In certain individuals, however, therapy is accompanied by adverse reactions. The mechanisms underlying these reactions are not yet known. The aim of the present study was to investigate whether neutrophils are involved in the development of these adverse reactions. Elastase and lactoferrin, two markers for the release of neutrophil azurophilic and specific granule contents respectively, were measured by radioimmunoassays in plasma of onchocerciasis patients with varying degrees of side effects, as well as in control subjects before and 1 and 2 days after ivermectin treatment. A considerable increase of elastase levels after treatment was observed, whereas lactoferrin levels did not change. The percentage of patients with elevated elastase levels was significantly correlated with the degree of side effects. These findings suggest that neutrophil activation may be involved in the development of adverse reactions in these patients.

Topics: alpha 1-Antitrypsin; Cell Degranulation; Drug Eruptions; Fever; Humans; Ivermectin; Lactoferrin; Lymphadenitis; Neutrophils; Onchocerciasis; Pancreatic Elastase; Pruritus

Topics: Aged; Blood Proteins; Chemotaxis, Leukocyte; Chromatography, Gel; Chronic Disease; Cytoplasmic Granules; Eosinophil Granule Proteins; Female; Granulocytes; Humans; Lactoferrin; Leukocyte Count; Muramidase; Neutrophils; Peroxidase; Pruritus; Ribonucleases