What is the role of cytokines in the pathogenesis of meningitis?

Updated: Jul 16, 2019
  • Author: Rodrigo Hasbun, MD, MPH; Chief Editor: Michael Stuart Bronze, MD  more...
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Answer

Increased CSF concentrations of TNF-α, IL-1, IL-6, and IL-8 are characteristic findings in patients with bacterial meningitis. Cytokine levels, including those of IL-6, TNF-α, and interferon gamma, have been found to be elevated in patients with aseptic meningitis.

The proposed events involving these inflammation mediators in bacterial meningitis begin with the exposure of cells (eg, endothelial cells, leukocytes, microglia, astrocytes, and meningeal macrophages) to bacterial products released during replication and death; this exposure incites the synthesis of cytokines and proinflammatory mediators. This process is likely initiated by the ligation of the bacterial components (eg, peptidoglycan and lipopolysaccharide) to pattern-recognition receptors, such as the Toll-like receptors (TLRs).

TNF-α and IL-1 are most prominent among the cytokines that mediate this inflammatory cascade. TNF-α is a glycoprotein derived from activated monocyte-macrophages, lymphocytes, astrocytes, and microglial cells.

IL-1, previously known as endogenous pyrogen, is also produced primarily by activated mononuclear phagocytes and is responsible for the induction of fever during bacterial infections. Both IL-1 and TNF-α have been detected in the CSF of individuals with bacterial meningitis. In experimental models of meningitis, they appear early during the course of disease and have been detected within 30-45 minutes of intracisternal endotoxin inoculation.


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