Inadequate host defenses may partly explain the problem of recurrent peritonitis in patients on continuous ambulatory peritoneal dialysis. It has been suggested that these defenses may be adversely affected by the fluids used for dialysis, and so we examined the effects of unused, effluent, and infected peritoneal dialysis fluids on phagocytosis and killing by normal neutrophils. We used a clinical isolate of Staphylococcus epidermidis as the test organism, as this organism is the most commonly cultured in continuous ambulatory peritoneal dialysis peritonitis; we also used a fungal species, Candida guilliermondii. There was no phagocytosis of either organism in unused dialysate because of lack of opsonins and low pH. Phagocytosis in effluent dialysate did not occur because of inadequate opsonin levels and was variable in infected effluents, depending on quantities of immunoglobulins present. Intracellular killing of both test organisms was normal in unused dialysate in the presence of 5 % normal serum, but was reduced in effluent and infected dialysates because of factors inhibiting killing by neutrophils. These factors adversely affected the killing of S. epidermidis more than that of C. guilliermondii. These results may explain why peritonitis recurs, particularly peritonitis due to S. epidermidis, because organisms could be sequestered within the neutrophils and thus be protected from antibiotic action. Reinfection of the peritoneal cavity would then take place following neutrophil breakdown, causing a clinical relapse.

Frequent and recurrent episodes of peritonitis are a major cause of morbidity in patients on continuous ambulatory peritoneal dialysis (CAPD). One factor contributing to this problem may be an abnormality of neutrophil function in these patients. We have therefore quantified phagocytosis and killing by circulating and peritoneal neutrophils from patients on CAPD with and without peritonitis. Circulating neutrophils from uninfected patients showed reduced phagocytosis of both Staphylococcus epidermidis and Candida guilliermondii because of an opsonic defect in CAPD serum and because of a defect of the neutrophils themselves. In contrast, phagocytosis by circulating and peritoneal neutrophils from patients with peritonitis was normal. Intracellular killing of C. guilliermondii was normal in all groups of neutrophils but killing of S. epidermidis, the organism most commonly isolated in CAPD peritonitis, was reduced. The possible mechanisms for the enhanced neutrophil activity seen in peritonitis, and for the decreased killing of S. epidermidis in contrast to normal killing of C. guilliermondii are discussed. A defect in killing of S. epidermidis may explain why peritonitis caused by this organism can be difficult to erradicate.

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To investigate the role of neutrophils in complement-induced changes in vascular permeability, skin wheal and flare responses to intradermal injection of autologous activated serum complement were measured in normal and neutropenic subjects. In normal subjects, responses were dose-dependent and were abolished by removal of C5 from serum. Biopsy of a wheal revealed neutrophils adherent to vascular endothelium. In neutropenic subjects (neutrophil count less than 0.5 X 10(9)/l), responses to complement-activated serum or a low molecular weight fraction from it were significantly reduced. This could not be accounted for by a reduction in concentration of C5 conversion products. In one subject with chronic granulomatous disease a normal response was produced. Local injection of the anti-histamine (H1) drug clemastine produced only partial inhibition of responses, while almost totally abolishing histamine-induced wheals. Systemic anti-inflammatory drugs had no effect. The data suggest that the microvascular response to activated complement in man is at least partly due to an interaction between C5 fragments and neutrophils.

Human neutrophil cobalamin binding protein (NCBP) is located exclusively in the neutrophil secondary granules. The soluble stimuli formlymethionyl-leucyl-phenylalanine and the low-molecular-weight complement fragment C5a both promote the dose-dependent release of NCBP from cytochalasin B-treated neutrophils in vitro. The extracellular discharge of NCBP induced by higher secretagogue is inhibited by prior exposure of neutrophils to the corticosteroids hydrocortisone and methylprednisolone and the nonsteroidal antiinflammatory agents indomethacin and ibuprofen. The four antiinflammatory agents function as competitive antagonists of neutrophil secondary granule discharge with a site of action at or near the cell surface. These findings support the hypothesis that antiinflammatory agents prevent neutrophil activation in vitro by inhibition of stimulus-receptor coupling. The significance of these observations with regard to the in vivo actions of these agents remains uncertain, however.