BORRELIA-BURGDORFERI INDUCES CHEMOKINES IN HUMAN MONOCYTES

Lyme disease is clinically and histologically characterized by strong inflammatory reactions that contrast the paucity of spirochetes at les ional sites, indicating that borreliae induce mechanisms that amplify the inflammatory response. To reveal the underlying mechanisms of chem oattraction and activation of responding leukocytes, we investigated t he induction of chemokines in human monocytes exposed to Borrelia burg dorferi by a dose-response and kinetic analysis. Lipopolysaccharide (L PS) derived from Escherichia coil was used as a positive control stimu lus. The release of the CXC chemokines interleukin-8 (IL-8) and GRO-al pha and the CC chemokines MIP-1 alpha, MCP-1, and RANTES was determine d by specific enzyme-linked immunosorbent assays, and the correspondin g gene expression patterns were determined by Northern blot analysis. The results showed a rapid and strong borrelia-inducible gene expressi on which was followed by the release of chemokines with peak levels af ter 12 to 16 h. Spirochetes and LPS were comparably effective in stimu lating IL-8, GRO-alpha, MCP-1, and RANTES expression, whereas MIP-1 al pha production preceded and exceeded chemokine levels induced by LPS. Unlike other bacteria, the spirochetes themselves did not bear or rele ase factors with intrinsic chemotactic activity for monocytes or neutr ophils. Thus, B. burgdorferi appears to be a strong inducer of chemoki nes which may, by the attraction and activation of phagocytic leukocyt es, significantly contribute to inflammation and tissue damage observe d in Lyme disease.