Measurement of Levels of Tumor Necrosis Factor-  and Interleukin-1  in the CSF of Patients with Meningitis of Different Etiologies: Utility in the Differential Diagnosis

Abstract

We assayed tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) concentrations in CSF from patients with meningitis of different etiologies and tested the usefulness of these assays for differentiating between pyogenic meningitis and aseptic meningitis of different etiologies. We used a monoclonal-antibody ELISA to test 125 CSF specimens from patients whose cases were classified as follows: pyogenic meningitis (n = 20), viral meningitis (n = 22), self-resolving aseptic meningitis for which no specific diagnosis was made (n = 25), meningitis due to other infectious agents (n = 11), and neoplastic meningitis (n = 5); we also tested normal CSF from healthy patients (n = 20) and those with neurological diseases (n = 22). Levels of TNF-alpha were above 200 pg/mL in 16 of 20 patients with pyogenic meningitis, but not in patients in the other groups. Levels of IL-1 beta were above 100 pg/mL in 15 of 20 patients with pyogenic meningitis and in one patient with a brain abscess. A positive correlation between levels of these cytokines and different inflammatory parameters was noted, whereas an inverse relationship with the duration of symptoms was observed. With regard to diagnosis, measurement of TNF-alpha and IL-1 beta levels showed sensitivities of 84.2% and 78.9%, respectively; specificities of 100% and 99%, respectively; a positive predictive value of 1 and 0.93, respectively; and a negative predictive value of 0.97 and 0.96, respectively.

Lack of value of routine analysis of cerebrospinal fluid for prediction and diagnosis of external drainage–related bacterial meningitis

“…10,12 Lopez-Cortes and colleagues 11 found that CSF levels of tumor necrosis factor-␣, IL-1␤, IL-6, and IL-8 were significantly higher in neurosurgical patients with bacterial meningitis than in patients with asymptomatic aseptic meningitis. These inflammatory cytokines are synthesized intrathecally by activated leukocytes 7,24 and were found to be more specific predictors of bacterial meningitis, compared with cell counts, in the study by Lopez-Cortes and colleagues.…”

Update on Meningococcal Disease with Emphasis on Pathogenesis and Clinical Management

“…Once in the subarachnoid space, where the principal humoral and cellular host defense mechanisms are absent (432,555), meningococci proliferate uncontrolled (57). The evolving endotoxin liberation elicits compartmentalized (i.e., confined to the subarachnoid space) activation of proinflammatory cytokines such as TNF, IL-1, IL-6, IL-8, nitric oxide, monocyte colony-stimulating factor, and platelet-activating factor and anti-inflammatory cytokines such as IL-1Ra, IL-10, IL-12, TNFsR-p55, TNFsR-p75, and IL-1sR type II (IL-1sRII) (12,57,192,264,295,429,498,502,517,(519)(520)(521). Among these, TNF and IL-1 enhance the permeability of the blood-brain barrier and promote the influx of neutrophils by upregulation of adherence molecules (258,374,377,428).…”

Rapid induction of tumor necrosis factor alpha in the cerebrospinal fluid after intracerebroventricular injection of lipopolysaccharide revealed by a sensitive capture immuno-PCR assay.

“…However, the vaccine had little impact on the incidence of bacterial meningitis at large (8,9). TNF-a has been detected in the cerebrospinal fluid (CSF) of the majority of patients with bacterial meningitis and in some patients with viral forms (10)(11)(12). Furthermore, CNS damage in the course of bacterial meningitis correlates with the extent of the inflammatory response in the subarachnoid space (13,14).…”