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Critical illness is an aetiologically and clinically heterogeneous syndrome that is characterised by organ failure and immune dysfunction. Mortality in critically ill patients is driven by inflammation-associated organ damage and a profound vulnerability to nosocomial infection. Both factors are influenced by the activated complement protein C5a, released by unbridled activation of the complement system during critical illness. C5a exerts deleterious effects on organ systems directly and suppresses antimicrobial functions of key immune cells. Whilst several recent reports have added key knowledge of the cellular signalling pathways triggered by C5a, there remain a number of areas that are incompletely understood and therapeutic opportunities are still being evaluated. In this review, we summarise the cellular basis for C5a-induced vulnerability to nosocomial infection and organ dysfunction. We focus on cells of the innate immune system, highlighting the major areas in need of further research and potential avenues for targeted therapies.

Neutropenia, neutrophil dysfunction, and recurrent infections are important manifestations of glycogen storage disease type Ib. We report here a child who has had adequate metabolic control, but developed brain abscess, an infection not previously described in this disease. This case provides further evidence that the neutrophil anomaly is related to the basic enzyme defect, not secondary to the metabolic derangement.

Infections are still a major cause of morbidity and mortality in end-stage renal disease (ESRD) patients. The susceptibility of ESRD patients to infections is typically ascribed to the immunodeficient state associated with uremia. A central role in the host defense against bacterial infections is played by phagocytic polymorphonuclear white blood cells, which are characterized by the capacity to ingest and subsequently destroy bacteria. Disorders in polymorphonuclear cell function are exacerbated by the dialysis procedure and numerous factors including uremic toxins, iron overload, anemia of renal disease, and dialyzer bioincompatibility. It is concluded that the phagocytic defect observed in ESRD is multifactorial, and each factor should be managed individually with specific therapeutic approaches.

Experimental diabetes is one of the most popular conditions in which to study the relation between neutrophil leukocyte activity and periodontal destruction. The aetiology of neutrophil dysfunction in the gingival tissue associated with diabetes has yet to be clarified. Diabetes in rats decreases neutrophil chemotactic activity in proportion to the severity of this systemic disorder. The present study was carried out to evaluate the relationship between the severity of diabetes and the neutrophil response to two chemotactic agents, and to correlate the observed neutrophil defects with the degree of diabetes. In this study two chemotactic agents, casein (0.2 μl, 2 mg ml−1) or N-formylmethionylleucylphenylalanine (FMLP; 0.2 μl, 10−4 M), were placed into the gingival crevices of alloxan-induced diabetic rats. Gingival biopsies were taken 15 min later and then at 5-min intervals up to 45 min and investigated by electron microscopy. Adherence and migration were observed in the rats with moderate diabetes 30 min after the application of casein. There was chemotaxis after 35 min of administration of the peptide FMLP. By 40 min neutrophils with pyknotic nuclei were observed. At 45 min neutrophils with a decreased number of granules were present. As the severity of the diabetes increased, the neutrophils degenerated and were structurally distorted. In the rats which had alloxan-induced diabetes there was abnormal periodontal damage. This damage is thought to be related to dysfunctional neutrophils. These findings many contribute to an answer to the following question: why is there an apparent variability in the susceptibilty of periodontal breakdown in diabetics? Copyright © 2003 John Wiley & Sons, Ltd.

Spontaneous and endotoxin-stimulated nitroblue tetrazolium (NBT) dye reduction was evaluated in 86 individuals cured of various types of solid malignancies and in 55 healthy adults. Oxygen consumption tests, at rest and during phagocytosis, were performed with polymorphonuclear leukocytes of 22 patients and 10 controls, chosen at random. The results revealed an impaired capacity of patients' neutrophils to reduce NBT. The decrease in the stimulated reduction values was more pronounced (p less than 0.0005) than in spontaneous values (p less than 0.01), and was also noticed in patients who had been treated by surgery alone and in those with a disease-free interval of 10 years or more. Oxygen consumption by patients' leukocytes was similar to that of controls. The present results, especially those of the endotoxin-stimulated NBT test, might reflect a neutrophil dysfunction in cured cancer patients. The nature of such an abnormality and its possible clinical implication are still obscure.

Summary The functions of neutrophils obtained from 3 calves affected with chronic and recurrent pneumonia, with marked neutrophilia, were examined. Their functions were compared with those of normal calves. Neutrophils from the three calves showed a markedly decreased phagocytosis, bacterial killing activity, NBT reduction activity, luminol-dependent chemiluminescence and chemotactic response. These findings show that the 3 calves had defective neutrophils; the disorder was diagnosed as bovine granulocytopathy syndrome. Zusammenfassung Bovines Granulozytopathie-Syndrom: Dysfunktion der neutrophilen Granulozyten bei Holstein-Friesian-Kalbern: Es wurde die Funktion von neutrophilen Granulozyten gepruft, die von 3 Kalbern mit chronischer recurrenter Pneumonie und ausgepragter Neutrophilie stammten. Zum Vergleich wurde auch die Funktion neutrophiler Granulozyten von normalen Kalbern untersucht. Die von den drei kranken Kalbern stammenden neutrophilen Granulozyten zeigten eine herabgesetzte Phagozytose, eine verringerte Bakterien-Abtotungs-Aktivitat, eine verringerte NBT-Reduktions-Aktivitat, eine herabgesetzte Luminol-abhangige Chemohumineszenz sowie eine reduzierte chemotaktische Antwort. Nach diesen Befunden hatten die 3 Kalber defekte neutrophile Granulozyten; die Storung wurde als bovines Granulozytopathie-Syndrom diagnostiziert.

Leukocyte chemotaxis (in five patients with pyoderma gangrenosum) was studied using a modification of the Boyden chamber method. In all patients the chemotactic response was significantly lower than in the controls. This abnormal chemotaxis was a result of an intrinsic neutrophil dysfunction. No significant difference was detected between the chemotactic response of leukocytes from patients with minimal or no skin involvement and those from patients with extensive lesions.