Roles of proinflammatory and anti-inflammatory cytokines in pathophysiology of bacterial meningitis and effect of adjunctive therapy

Since meningitis is an inflammation in a closed space, i.e., the skull, without any possibility for expansion, deleterious effects on the CNS can occur rather rapidly. Bacteria and bacterial products stimulate the production of proinflammatory and anti-inflammatory cytokines and prostaglandins in the CNS, all of which have an effect on the occurrence of inflammatory exudate. Therefore, it might be preferable to choose antibiotics that cause the least release of cell wall components in order to avoid the production of proinflammatory mediators. Many modalities to limit the inflammatory process have been studied. Immunotherapy with MAb or anti- inflammatory cytokines are successful in experimental meningitis but have not yet reached the level of clinical research. In experimental meningitis some nonsteroidal anti-inflammatory drugs (NSAIDs) have shown beneficial effects on CNS inflammation while others have not (42, 136, 142). At the moment it is unpredictable which NSAIDs can safely be administered to patients with meningitis. PTX inhibits the production of various cytokines and has a favorable effect on the course of experimental meningitis but, as far as we know, has not yet been used in patients with meningitis. Studies with experimental meningitis and clinical trials have shown that GC are the most promising drugs for adjunctive therapy. DXM has a beneficial effect on the neurologic and audiologic outcome of the disease. Preferably, the first dose of DXM must be administered before or with the first dose of the antibiotic. Since in experimental meningitis, PTX reduced the inflammation in the gAS markedly, it may be assumed that DXM in combination with PTX would have a favorable result through the inhibition of proinflammatory mediators. The fact remains, however, that more clinical studies with various adjunctive drugs alone and in combination must be performed before firm recommendations can be made.