Interleukin-10 and Soluble Tumor Necrosis Factor Receptors in Cerebrospinal Fluid of Children with Bacterial Meningitis

Abstract

The antiinflammatory mediators interleukin (IL)-10 and soluble tumor necrosis factor (TNF) receptors p55 (sTNFR-55) and sTNFR-75 in cerebrospinal fluid (CSF) from 37 children with bacterial meningitis were studied. CSF concentrations of IL-10, sTNFR-55, and sTNFR-75 and of the proinflammatory cytokines TNF-alpha, IL-6, and IL-8 were markedly elevated and were, with the exception of the sTNFRs, significantly higher in CSF than in serum. CSF concentrations of sTNFR- 55 and sTNFR-75 were only associated positively with IL-10 levels. CSF glucose levels correlated highly with levels of IL-10, sTNFR-55, and sTNFR-75 and weakly with TNF-alpha and IL-6. Cytokine levels in CSF decreased rapidly, while sTNFR levels remained elevated for at least 24 h.

Systemic Neutralization of Interleukin-8 Markedly Reduces Neutrophilic Pleocytosis during Experimental Lipopolysaccharide-Induced Meningitis in Rabbits

“…3.89 to 389 ng/ml of CSF) were injected in order to span the concentration ranges determined in clinical specimens (ca. 0.02 to 150 ng/ml of CSF) (7,19,26,29,39,46,49,51,57,58,62). Figure 2 demonstrates that, during an 8-h period after the intracisternal injection of 1,750 ng of hIL-8, no influx of leukocytes or accumulation of TNF or of total protein occurred in the CSF.…”

“…Furthermore, a recent study demonstrated a correlation between CSF IL-8 levels and neutrophil levels of samples obtained within 12 h of the onset of aseptic meningitis (62). In those clinical studies considering cytokine determinations from sequential samples (26), CSF IL-8 concentrations decreased with the commencement of disease resolution. Many chemotactic peptides can be detected in the CSF of meningitis patients.…”

“…Many clinical studies have detected IL-8 in the CSF of meningitis patients (7,19,26,29,39,46,49,51,57,58,62), suggesting that this chemokine may play a role in the accumulation of neutrophils within the subarachnoid space. Clinically, there appears to be a marked difference in the duration of elevated chemokine levels between tubercular and acute bacterial meningitis, with the former displaying protracted elevated chemokine levels compared to the latter (32).…”

“…Clinically, there appears to be a marked difference in the duration of elevated chemokine levels between tubercular and acute bacterial meningitis, with the former displaying protracted elevated chemokine levels compared to the latter (32). Some (39,51) but not all (7,19,26,29,49) of these clinical studies were able to correlate the CSF IL-8 concentration to neutrophil levels during bacterial meningitis, but this conclusion needs to viewed cautiously since many of these clinical samples were from single time points at indeterminate times after the induction of pleocytosis. However, there is some evidence that CSF samples obtained within 12 h of onset of clinical symptoms have higher CSF IL-8 levels than in those obtained later in the clinical course (19).…”

Pathophysiology of acute meningitis caused by Streptococcus pneumoniae and adjunctive therapy approaches

“…IL-10 is a potent immunosuppressive cytokine, produced by monocytes, macrophages, B and T lymphocytes, brain cells such as neurons and microglia 41 . Elevated levels have been found in the CSF in patients with bacterial meningitis 42 , it leads to macrophage and monocyte deactivation and inhibits the cytokines production such as TNF-α and IL-6 and the release of reactive oxygen species 43 . IL-10 gene-deficient mice were associated with higher levels of TNF-α and IL-6 in animal model of pneumococcal meningitis 36 .…”