Lipopolysaccharide (LPS) is a potent chemotactic component for polymorphonu
clear leukocytes (PMN, neutrophils). Since LPS tolerance was first describe
d, many studies have been reported about the hyporesponsiveness bl vitro co
rresponding to attenuating: production of proinflammatory cytokines.
We hypothesized that in vivo daily exposure to LPS stimuli impairs neutroph
il accumulation in the rat airway. Interleukin 8 (IL-8) and/or CXC-chemokin
e, a neutrophil chemoattractant and activating cytokine, have been implicat
ed as proinflammatory mediators in gram-negative respiratory tract infectio
ns. It is possible that the tolerance to LPS has occurred in relation to th
is chemoattractant cytokine production.
To settle this issue, we examined whether the neutrophil count in bronchoal
veolar lavage fluid (BALF) decreases after daily inhalation of Pseudomonas
aeruginosa LPS into the rat airway.
Repeated inhalation of LPS into the airway resulted in reduction in neutrop
hil recruitment. We measured rat CXC-chemokine (rat GRO/CINC1) levels in re
covered BALF. There were noted reductions of rat GRO corresponding to the d
iminished neutrophil trafficking. We also confirmed that the HLA DR positiv
e lymphocyte number in BALF gradually increased after daily inhalation of L
PS.
These results suggest that continuous stimuli of LPS mitigate the accumulat
ion of inflammatory cells in the airway by reducing chemokine production wi
th a consequent change in the appearance of local inflammation to a chronic
state.