[Modern concepts of anti-inflammatory therapy in bacterial meningitis].

Pathophysiologic disorders in bacterial meningitis and their influence on the course and prognosis of the disease are analysed. Deterioration of the CNS is due to inflammatory response of the host combined with other pathophysiological disorders. Inflammatory response in the subarachnoid space is the most intensive, but the most deleterious, as well, in the first several hours of antibiotic therapy when bacterial disintegration ensues. Fragments of the cell wall and endotoxin are very active components, independent of the presence of living bacteria in the subarachnoid space. Each microorganism induces different inflammatory response, and the course of the disease is, therefore, also different. Bacterial disintegration reta and release of the components are determined by the intensity of the inflammatory response in the subarachnoid space. Which, in turn, determine the degree of tissue damage. Bacterial products stimulate release of inflammatory mediators--cytokines from macrophages and other sources. Local production of cytokines from astrocytes and macroglial cells (macrophage equivalents in the CNS) is the first stage in development of the inflammatory response and tissue destruction. Cytokines induce damage of the CNS by attracting the inflammatory cells and by releasing superoxide anions inducing arachidonic acid metabolism and production of vasoactive metabolites of arachidonic acid which result in damage of blood-brain barrier, having, therefore, a direct cytotoxic effect. Consequences of these pathophysiologic disorders are cerebral oedema and elevated intracranial pressure. Current concepts of antiinflammatory therapy are, in the light of pathophysiological events in the CNS, directed to interruption of cytokine activation (steroids), prevention of production of vasoactive arachidonic acid metabolites (non-steroidal agents), and prevention of leukocyte transfer into the subarachnoid space (antileukocyte, anti-integrin antibodies).