Pseudomonas aeruginosa (P. aeruginosa) is the major pathogen in nosocomial and life-threatening
infections of immunocompromised or
critically ill patients. The macrophage-activating lipopeptide-2 (MALP-2) activates the immune system via
Toll-like receptors (TLR) 2 and 6 and leads to an accumulation of immune cells in lungs of young adult (8-10 week old) rats after intratracheal application. This is characterized by a high increase of granulocyte numbers in the BAL 24 h after
MALP-2 treatment. It was hypothesized that
MALP-2 may have a positive effect on the
clinical course of an experimental
infection. Therefore, rats were treated with
MALP-2 at different time points following an
infection with P. aeruginosa. The effect of
MALP-2 in combination with immunization with inactivated P. aeruginosa was also investigated. Rats (n = 10) were infected intratracheally (i.t.) with 1 x 10(8) CFU P. aeruginosa on day 0. They were treated on day -3, -1, 0 and +1 with 2.5 microg
MALP-2 or the vehicle i.t. In additional experiments, rats were immunized on day -21 and -14 with 1 x 10(8) CFU of inactivated P. aeruginosa bacteria and 2.5 microg
MALP-2 or vehicle with 1 x 10(8) CFU of inactivated bacteria and
isopropanol. The clinical score, rectal temperature and weight of the rats were checked in both treatment and immunization experiments twice a day. On day 2 they were sacrificed, CFU were determined in the left lung, the right lung being used for histology. In the group treated with
MALP-2 1 day prior to
infection significant effects were seen: The rectal temperature was about 2 degrees C higher in comparison to the controls at 6 h and also 1 day after
infection. Both the symptoms of the
infection and the
weight loss were significantly reduced. In addition, the CFU and the
inflammation in the lung tissue were significantly lower. These effects were not observed
after treatment on day -3, 0 or +1. The
MALP-2 enhanced immunization only resulted in a tendency to clinical improvement. In conclusion, local immunostimulation at the appropriate time can enhance the host defense against bacteria in the lung.