CHEMOTACTIC ACTIVITY ON MONONUCLEAR-CELLS IN THE CEREBROSPINAL-FLUID OF PATIENTS WITH VIRAL MENINGITIS IS MEDIATED BY INTERFERON-GAMMA INDUCIBLE PROTEIN-10 AND MONOCYTE CHEMOTACTIC PROTEIN-1

In viral meningitis the inflammatory response involves activated T cel ls and monocytes which are recruited into the subarachnoid space. To i dentify the chemotactic signals attracting the cells to the site of in fection in the meninges, we measured the levels of two CXC chemokines, interferon-gamma (IFN-gamma) inducible protein (IP)-10 and monokine i nduced by IFN-gamma, four CC chemokines, monocyte chemotactic protein (MCP)-1, RANTES, macrophage inflammatory protein (MIP)-1 alpha and MIP -1 beta, as well as the cytokines interleukin (IL)-15 and IL-16 in the cerebrospinal fluid (CSF) of patients suffering from viral meningitis . The results point to an involvement of two chemokines, MCP-1 and IP- 10, since (1) unlike the other cytokines, MCP-1 and IP-10 were present in 97% and 79% of the CSF, respectively, at concentrations sufficient to induce chemotaxis of mononuclear cells; (2) more than 90% of the C SF of viral meningitis induced chemotaxis of peripheral blood mononucl ear cells (PBMC) and all of them induced chemotaxis of activated T cel ls, and (3) the CSF-mediated chemotaxis of PBMC was inhibited by anti- MCP-1 antibodies and chemotaxis of activated T cells was abolished by the combination of anti-MCP-1 and anti-IP-10 antibodies. Our data prov ide evidence that MCP- and IP-10 lead to accumulation of activated T c ells and monocytes in the CSF compartment in viral meningitis.