Interestingly, in contrast to Gram-positive pneumonia, preliminary data from our laboratory reveal that RAGE plays a benefi cial role in mice during the host response to Gram-negative pneumonia (unpublished data). Indeed, RAGE defi ciency was associated with increased mortality and increased bacterial outgrowth and dissemination after K. pneumoniae inoculation (unpublished data). Relative to wild type mice, lung infl ammation was similar and cytokine and chemokine levels were slightly -if at allelevated. Moreover, RAGE -/mice showed an unaltered response to intranasally instilled Klebsiella LPS with respect to pulmonary cell recruitment and local release of cytokines and chemokines. Together, these fi ndings indicate that RAGE contributes to an eff ective antibacterial host response during K. pneumoniae pneumonia, whereas RAGE plays an insignifi cant part in the lung infl ammatory response to either intact Klebsiella or Klebsiella LPS.