Vaccination promotes TH1-like inflammation and survival in chronic Pseudomonas aeruginosa pneumonia. A new prophylactic principle
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Vaccination promotes TH1-like inflammation and survival in chronic Pseudomonas aeruginosa pneumonia. A new prophylactic principle. / Johansen, H K; Cryz, S J; Hougen, H P; Moser, C; Høiby, N.
In: Behring Institute Mitteilungen, No. 98, 1997, p. 269-73.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Vaccination promotes TH1-like inflammation and survival in chronic Pseudomonas aeruginosa pneumonia. A new prophylactic principle
AU - Johansen, H K
AU - Cryz, S J
AU - Hougen, H P
AU - Moser, C
AU - Høiby, N
PY - 1997
Y1 - 1997
N2 - The ongoing lung tissue damage in chronically Pseudomonas aeruginosa infected cystic fibrosis (CF) patients has been shown to be caused by elastase liberated from polymorphonuclear leukocytes (PMN), which dominate the chronic inflammation in these patients. Most CF patients, however, contract the chronic lung infection with P. aeruginosa after a one-year period (median) of intermittent colonization. Therefore, prevention of the onset of the chronic infection or prevention of the dominance of the inflammation by PMNs would be important goals for a vaccine strategy against P. aeruginosa in CF. In a rat model of acute P. aeruginosa pneumonia we studied whether it was possible to improve the initial bacterial clearance and diminish the inflammatory response by vaccination prior to challenge with free, live P. aeruginosa. The vaccines studied were PAO 579 sonicate, O-polysaccharide toxin A (TA) conjugate, depolymerized alginate (3064) TA conjugate (D-ALG TA), or P. aeruginosa alginate (6680 + 8839). The vaccines could, however, not improve the very efficient natural clearance of P. aeruginosa from the lungs of the rats. In a rat model of chronic P. aeruginosa lung infection we found that none of the vaccines could prevent chronic lung inflammation. After challenge, however, none of the rats immunized with D-ALG TA died in contrast to the other vaccine groups combined (p = 0.03). In addition, the inflammatory response changed from an acute type inflammation dominated by PMNs as in CF patients to a chronic type inflammation dominated by mononuclear leukocytes. This response was achieved within the first week after challenge in D-ALG TA immunized rats; in the controls, the inflammation was still acute 4 weeks after challenge. Rats immunized with D-ALG TA had a significantly reduced severity of the macroscopic lung inflammation compared to the other vaccination groups (p = 0.009). The same effect could be obtained by IFN-gamma treatment (p = 0.004). The chronic P. aeruginosa lung infection was established in two inbred mice strains C3H/HeN, known as TH1 responders, and Balb/c, known as TH2 responders. The mortality due to the infection was significantly lower in C3H/HeN mice compared to Balb/c mice (p <0.0003). P. aerurinosa was cleared more efficiently by C3H/HeN mice and significantly more C3H/HeN mice showed normal lung histopathology than Balb/c mice (p <0.025). Supernatants from Concanavalin A stimulated spleen cells from C3H/HeN mice contained three times higher IFN-gamma concentration but only half as high interleukin-4 concentration than those of Balb/c mice. These findings suggest that change from the TH2-like response seen in CF patients towards a TH1 response might improve their prognosis.
AB - The ongoing lung tissue damage in chronically Pseudomonas aeruginosa infected cystic fibrosis (CF) patients has been shown to be caused by elastase liberated from polymorphonuclear leukocytes (PMN), which dominate the chronic inflammation in these patients. Most CF patients, however, contract the chronic lung infection with P. aeruginosa after a one-year period (median) of intermittent colonization. Therefore, prevention of the onset of the chronic infection or prevention of the dominance of the inflammation by PMNs would be important goals for a vaccine strategy against P. aeruginosa in CF. In a rat model of acute P. aeruginosa pneumonia we studied whether it was possible to improve the initial bacterial clearance and diminish the inflammatory response by vaccination prior to challenge with free, live P. aeruginosa. The vaccines studied were PAO 579 sonicate, O-polysaccharide toxin A (TA) conjugate, depolymerized alginate (3064) TA conjugate (D-ALG TA), or P. aeruginosa alginate (6680 + 8839). The vaccines could, however, not improve the very efficient natural clearance of P. aeruginosa from the lungs of the rats. In a rat model of chronic P. aeruginosa lung infection we found that none of the vaccines could prevent chronic lung inflammation. After challenge, however, none of the rats immunized with D-ALG TA died in contrast to the other vaccine groups combined (p = 0.03). In addition, the inflammatory response changed from an acute type inflammation dominated by PMNs as in CF patients to a chronic type inflammation dominated by mononuclear leukocytes. This response was achieved within the first week after challenge in D-ALG TA immunized rats; in the controls, the inflammation was still acute 4 weeks after challenge. Rats immunized with D-ALG TA had a significantly reduced severity of the macroscopic lung inflammation compared to the other vaccination groups (p = 0.009). The same effect could be obtained by IFN-gamma treatment (p = 0.004). The chronic P. aeruginosa lung infection was established in two inbred mice strains C3H/HeN, known as TH1 responders, and Balb/c, known as TH2 responders. The mortality due to the infection was significantly lower in C3H/HeN mice compared to Balb/c mice (p <0.0003). P. aerurinosa was cleared more efficiently by C3H/HeN mice and significantly more C3H/HeN mice showed normal lung histopathology than Balb/c mice (p <0.025). Supernatants from Concanavalin A stimulated spleen cells from C3H/HeN mice contained three times higher IFN-gamma concentration but only half as high interleukin-4 concentration than those of Balb/c mice. These findings suggest that change from the TH2-like response seen in CF patients towards a TH1 response might improve their prognosis.
KW - Animals
KW - Bacterial Vaccines
KW - Chronic Disease
KW - Cystic Fibrosis
KW - Disease Models, Animal
KW - Humans
KW - Inflammation
KW - Mice
KW - Pneumonia
KW - Pseudomonas Infections
KW - Pseudomonas aeruginosa
KW - Rats
KW - Survival Rate
KW - Th1 Cells
M3 - Journal article
C2 - 9382750
SP - 269
EP - 273
JO - Behring Institute Mitteilungen
JF - Behring Institute Mitteilungen
SN - 0301-0457
IS - 98
ER -
ID: 44354323