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Abstract: The pathophysiology underlying the high incidence of post-stroke infectious complications has not been fully understood. We measured the respiratory burst of neutrophils as an index of their bactericidal function in patients with haemorrhagic stroke, and we also measured the plasma concentrations of noradrenalin, cortisol and neutrophil function-related amino acids. Blood samples were obtained from patients who underwent emergency craniotomies for haemorrhagic stroke (n =11) or CT-guided stereotaxic aspiration of intracerebral haematomas (n =6). Neutrophils were isolated, and their chemiluminescence response to N-formyl-methionyl-leucyl-phenylalanine was measured. Healthy volunteers served as controls (n =15). In patients with stroke, the chemiluminescence response of the isolated neutrophils was significantly lower than in the controls, and it was significantly inversely correlated with the plasma noradrenalin concentration. By Day 30, this value approached control levels. Other parameters measured were not significantly correlated with the chemiluminescence response. Stroke-induced suppression of the neutrophil respiratory burst may be responsible for frequent post-stroke infectious complications. [Copyright &y& Elsevier]

Summary: N,N-Dialanyl protoporphyrin (PP(Ala)2) and diarginine diprotoporphyrinate (PP(Arg)2) are porphyrin photosensitizers that are currently being used in the photodynamic therapy (PDT) of cancer. In the present study, the effects of these agents on the neutrophil respiratory burst in vitro were investigated. In the case of non-stimulated neutrophils, the respiratory burst was significantly increased in the presence of PP(Ala)2 in concentration 5.0mg/l, while in the presence of PP(Arg)2 in the same concentration it did not change. By contrast, both photosensitizers decreased a respiratory burst by neutrophils stimulated with opsonized zymosan. Pre-irradiation of solutions of PP(Ala)2 and PP(Arg)2 with ultraviolet A did not alter the observed responses. The prooxidative effect of PP(Ala)2 is probably due to the stimulation of protein kinase C, which plays a key role in the respiratory burst of non-stimulated cells, whereas the antioxidant effect of both photosensitizers may be explained by their inhibitory effect on EGFR tyrosine kinase, which plays an important role in the respiratory burst of cells stimulated by opsonized zymosan. The lack of effect of the two dyes after UV-A pre-irradiation may be due to rapid self-quenching of UV-A-excited dye molecules to the ground state. The results of this study provide a starting point for experiments in animal models aimed at determining the clinical importance of the observed effects in cancer diagnosis and therapy. [Copyright &y& Elsevier]