Systemic neutralization of interleukin-8 markedly reduces neutrophilic pleocytosis during experimental lipopolysaccharide-induced meningitis in rabbits

Interleukin-8 (IL-8) is elevated in the cerebrospinal fluid (CSF) of patien ts with meningitis and is proposed to participate in subarachnoid-space ple ocytosis. However, intracisternal injection of IL-8 into rabbits failed to induce indices typical of meningitis (leukocyte, tumor necrosis factor, or protein accumulation in the CSF or histopathological changes), indicating t hat merely increasing the CSF level of this chemokine is insufficient to in duce inflammation in this anatomical site. IL-8 treatment did not affect in flammatory responses to subsequently intracisternally administered lipopoly saccharide (LPS). IL-8 was chemotactic for rabbit neutrophils in vitro, and subcutaneous injection of IL-8 (diluted in buffer or CSF) proved the in vi vo activity of this peptide and suggested the absence of an IL-8 inhibitor in normal rabbit CSF. LPS-dependent pleocytosis was only slightly diminishe d by intracisternally administered murine anti-rabbit IL-8 monoclonal antib ody (MAb) WS-4 but was dramatically reduced by intravenously administered M Ab. Therefore, elevated CSF IL-8 levels may contribute to, but cannot solel y account for, neutrophil influx into the subarachnoid space during meningi tis. However, inhibition of IL-8 activity of the bloodstream side of the bl ood-brain barrier effectively reduces pleocytosis, indicating a central rol e of IL-8 in neutrophil influx into CSF during bacterial meningitis. Thus, inhibition of IL-8 is a possible therapeutic target for adjunct treatment o f meningitis.