Trehalose 6,6 '-dimycolate (cord factor) of Mycobacterium tuberculosis induces corneal angiogenesis in rats

Neovascularization or angiogenesis is required for the progression of chron ic inflammation. The mechanism of inflammatory neovascularization in tuberc ulosis remains unknown. Trehalose 6,6'-dimycolate (TDM) purified from Mycob acterium tuberculosis was injected into rat corneas, TDM challenge provoked a local granulomatous response in association with neovascularization, Neo vascularization was seen within a few days after the challenge, with the ex tent of neovascularization being dose dependent, although granulomatous les ions developed 14 days after the challenge. Cytokines, including tumor necr osis factor alpha (TNF-alpha), interleukin-8 (IL-8), IL-1 beta, and vascula r endothelial growth factor (VEGF), were found in lesions at the early stag e (within a few days after the challenge) and were detectable until day 21, Neovascularization was inhibited substantially by neutralizing antibodies to VEGF and IL-8 but not IL-1 beta. Treatment with anti-TNF-alpha antibodie s resulted in partial inhibition. TDM possesses pleiotropic activities, and the cytokine network plays an important role in the process of neovascular ization.