C-X-C and C-C chemokines are expressed in the cerebrospinal fluid in bacterial meningitis and mediate chemotactic activity on peripheral blood-derived polymorphonuclear and mononuclear cells in vitro.
The appearance of polymorphonuclear and mononuclear leukocytes in the cerebrospinal fluid (csf) is an important hallmark of bacterial meningitis. Chemokines are candidate mediators of cell migration from blood into the subarachnoid space. Therefore, concentrations of C-X-C and C-C chemokines in the csf of patients with pyogenic meningitis were measured by ELISA. Highly significant elevations of chemokine levels in comparison with noninflammatory csf controls were found for IL-8 (median, 21.6 ng/ml; range, < 0.1 to 191.3), growth-related gene product alpha (median, 5.6 ng/ml; range, < 0.1 to 48.2), monocyte chemotactic protein-1 (median, 26.4 ng/ml; range, < 0.2 to 193.8), macrophage inflammatory protein-1 alpha (MIP-1 alpha; median, 1.8 ng/ml; range, < 0.5 to 18.0), MIP-1 beta (median, 10.6 ng/ml; range, < 0.3 to 84.4), but not for RANTES (regulated upon activation, normal T cell expressed and secreted). The csf of bacterial meningitis were chemotactic for neutrophils and mononuclear leukocytes. Correlation analysis demonstrated a strong association between individual chemokine levels and chemotactic activity mediated by csf. A significant reduction of neutrophil chemotaxis was obtained by anti-IL-8 and anti-growth-related gene product alpha Abs, and a reduction of mononuclear cell migration was achieved by a combination of anti-monocyte chemotactic protein-1, anti-MIP-1 alpha, and anti-MIP-1 beta Abs. Since no significant correlation was found between csf leukocyte counts and chemokine concentrations or chemotactic activity mediated by csf, additional factors influence the extent of pleocytosis in vivo.
Spanaus
K S
KS
Department of Internal Medicine, University Hospital, Zurich, Switzerland.
Nadal
D
D
Pfister
H W
HW
Seebach
J
J
Widmer
U
U
Frei
K
K
Gloor
S
S
Fontana
A
A
D000328:Adult; D000368:Aged; D018925:Chemokines / Q000096:biosynthesis* / Q000134:cerebrospinal fluid* / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D016920:Meningitis, Bacterial / Q000134:cerebrospinal fluid* / Q000276:immunology*; D008583:Meningitis, Haemophilus / Q000134:cerebrospinal fluid / Q000276:immunology; D008585:Meningitis, Meningococcal / Q000134:cerebrospinal fluid / Q000276:immunology; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects*; D011008:Pneumococcal Infections / Q000134:cerebrospinal fluid / Q000276:immunology
D018925:Chemokines