Browsing by Author "Sakiniene, Egidija 1962-"

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    Modulation of the inflammatory responses in Staphylococcus aureus arthritis and sepsis
    (1999) Sakiniene, Egidija 1962-
    Bacterial arthritis is a severe, rapidly progressing erosive disease with high mor-bidity and mortality. Staphylococcus aureus is the most common bacterium causing this ailment. Systemic antibiotic treat-ment, with or without drainage, is the dominant therapeutic procedure. However, despite the use of antimicrobial treatment, a mortality rate of up to 20% and joint destruction are typical. The host immune response accounts for many of the consequences of infection.Using the model of haematogenously acquired S. aureus arthritis and sepsis we analysed host response mechanisms, and performed therapeutic approaches. Manipulations directed towards mediators of inflammation affect the course of the disease. Inhibitors of nitric oxide synthase aggravated S. aureus arthritis, presumably by impairing bactericidal capacity of macrophages. Furthermore, complement depletion disturbed the opsonization of bacteria yielding impaired phagocytic activity of phagocytes, and interacted with the process of extravasation and migration of polymorphonuclear cells, thus aggravating the clinical course of the disease. Blocking of complement receptor 1 (CD35) induced an increased severity of arthritis, probably via vasodilatation and neutrophil migration/extravasation augmenting action. Treatment with heparin aggravated S. aureus arthritis, possibly interacting with the complement system and opsonophagocytosis. We provide the evidence that co-treatment of systemic corticosteroids with the conventional therapy of septic arthritis diminishes disability and severity of the disease and increases survival. This effect seems to be dependent on the downregulatory effect of corticosteroids on the proliferation/differentiation of lymphocytes.Altogether, this thesis adds to the comprehension of the overall complexity of immune responses during sepsis and septic arthritis and indicates potential therapeutic modalities.