Cathelicidin (LL-37) is an antimicrobial peptide, which plays a role in the innate host defense. It is upregulated in the presence of vitamin D and elevated concentrations have been reported in cerebrospinal fluid (CSF) from patients with bacterial meningitis (BM). The aim of this study was to assess CSF LL-37 concentrations in childhood BM on admission and during antimicrobial treatment, and to investigate whether they predict the outcome in BM.
CSF samples were collected on admission (CSF1) and 12-24 hours later (CSF2) from patients with BM during 1996-2003 in the Dominican Republic (n=101, median age 8 months); 24 had S. pneumoniae, 36 H. influenzae, 7 N. meningitidis, and in 34 the etiology remained unknown. CSF LL-37 concentrations were measured by ELISA: the results are given as medians with interquartile range (IQR). LL-37 concentration and the LL-37 CSF2/CSF1 -ratio were compared with biomarkers associated with inflammation and clinical outcome using Spearman and Mann-Whitney tests as appropriate.
LL-37 concentrations in CSF1 and CSF2 were 25.7 (IQR 91.5, N=91) ng/mL and 9.5 (IQR 43.4, N=77) ng/mL, respectively. They did not vary according to etiology, age, or serum vitamin D concentration, (p>0.05), but correlated with CSF white cell count and protein levels (in CSF1, Rho 0.528 and 0.618, p<0.0001 for each, respectively). A lower LL-37 CSF2/CSF1–ratio correlated with a higher (=better) Glasgow Outcome Scale (GOS) score (Rho, -0.36; p=0.009) and a decrease in LL-37 concentration correlated with optimal recovery (GOS=5, p=0.046). No similar association was seen with the change in CSF white cell count or protein level.
Our results suggest that CSF LL-37 may be used as a novel biomarker of the inflammatory process in BM. A decrease in CSF LL-37 in response to treatment likely signaled a more rapidly limiting disease process and was associated with a better outcome in childhood BM.
I. Roine, None
S. Andersson, None
J. Fernandez, None
H. Peltola, None
T. Pelkonen, None