The effect of cefodizime on phagocyte function in non-patient volunteers and patients with chronic renal failure. In vitro and ex vivo studies.
Cefodizime has previously been shown to possess a number of immunomodulating properties in vivo and in vitro using several different test systems. Since most in vitro studies have been performed with cells from normal individuals, we first investigated whether cells from chronic renal failure patients would respond in vitro to cefodizime in the same way as healthy subjects. Subsequently, we investigated the effect of cefodizime (10 g over 10 days in 2-g doses) on phagocyte function ex vivo in an open study of 26 chronic renal failure patients and 16 healthy subjects. Polymorphonuclear leukocytes were tested for their ability to polarize in response to cefodizime and/or f-met-leu-phe peptide. Polymorphonuclear leukocytes and monocytes were tested for their ability to produce chemiluminescence on stimulation with either phagocytic (zymosan) or soluble phorbol myristate acetate stimuli. Phagocyte and lymphocyte membrane receptor expression was compared after exposure to cefodizime. Exposure to cefodizime in vitro causes a significant increase in polarization of polymorphonuclear leukocytes from both normal individuals and renal failure patients (both P < 0.001). It also caused increased chemotaxis and chemokinesis in a modified Boyden chamber assay. Cefodizime did not affect lucigenin-enhanced chemiluminescence and there were only minor effects on cell membrane antigen levels. In the ex vivo study there was a significant increase in polymorphonuclear leukocyte polarization (P < 0.001) attributable to cefodizime, but other investigations showed no significant differences. The results suggest that cefodizime may act as a mild priming agent for some functions, particularly chemotaxis.
McCafferty
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AC
Knight Scientific Ltd., The Laboratory, Plymouth, UK.
McGregor
E
E
Jones
M
M
Henderson
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IS
Cree
I A
IA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002439:Cefotaxime / Q000031:analogs & derivatives* / Q000494:pharmacology; D016764:Cell Polarity / Q000187:drug effects; D002511:Cephalosporins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007676:Kidney Failure, Chronic / Q000276:immunology* / Q000378:metabolism; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D010586:Phagocytes / Q000187:drug effects* / Q000276:immunology; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism
D002511:Cephalosporins; D011956:Receptors, Cell Surface; D002439:Cefotaxime; C033356:cefodizime