Bacterial meningitis: Mechanisms of disease and therapy

Abstract

Bacterial meningitis continues to be a serious infectious disease with a high morbidity and mortality in young children. Early recognition and initiation of adequate treatment are the major determinants for a good outcome. Recent advances in our understanding of the host inflammatory response by cytokines may result in the use of new therapeutic strategies. Such modulation of the inflammatory response may reduce the incidence of sequelae and death. The use of steroids as adjunctive therapy in children with bacterial meningitis probably has beneficial effects although the available data are still controversial. Additionally, studies in experimental meningitis models indicate that non-steroidal anti-inflammatory drugs and monoclonal antibodies against bacterial products, cytokines and CD18 on leucocytes reduce the extent of the meningeal inflammation. Human studies to evaluate the efficacy of these immune modulators are expected to start soon. However, prevention of bacterial meningitis by conjugate vaccines against Streptococcus pneumoniae and Neisseria meningitidis will be the most promising development in the next decade.

Immunoglobulin A1 Protease, an Exoenzyme of Pathogenic Neisseriae, Is a Potent Inducer of Proinflammatory Cytokines

“…A hallmark of the pathophysiology in these diseases is the intense inflammatory response associated with the substantial release of proinflammatory cytokines. TNF-␣, IL-1, IL-6, and IL-8 have been detected in local secretions and sera during mucosal infections with gram-negative species, including N. meningitidis and N. gonorrhoeae (29,35). Increased levels of IL-8 and TNF-␣ in particular in plasma and in urine, and smaller amounts of IL-1␤ and IL-6 were found in experimental gonorrhea after intraurethral application of gonococci (32).…”

“…They promote local inflammatory responses at the sites of microbial infections, and mediate adherence of leukocytes to the endothelial tissues and their transmigration by upregulating the expression of adhesion molecules (24)(25)(26)(27). Elevated levels of TNF-␣ , IL-1, IL-6, and IL-8 have been found in the cerebrospinal fluid (CSF) 1 and plasma of patients with meningitis (28)(29)(30)(31) and were detected in the urine after the intraurethral challenge of patients with N. gonorrhoeae (32).…”

Mechanisms of multidrug transporters

“…All together, these diseases are responsible for millions of deaths yearly. Several reports have also indicated the clinical importance of drug resistance in the treatment of meticillin‐resistant Staphylococcus aureus [9–11], Escherichia coli infections [12], and bacterial meningitis [13]. Drug resistance is difficult to control in hospital environments due to the limited number of effective agents that are available.…”

Intrathecal production of interleukin-12 and gamma interferon in patients with bacterial meningitis

“…Proinflammatory cytokines (tumor necrosis factor alpha [TNF-␣], interleukin-6 [IL-6], IL-8, and gamma interferon [IFN-␥]) are involved in the pathophysiology of bacterial meningitis (18). Recently, a novel cytokine with proinflammatory effects has been described (10,17,26,31).…”