Abstract
In a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis (CF) we studied whether the inflammatory response could be altered by vaccination. Rats were immunized with either a depolymerized alginate toxin A conjugate (D-ALG toxin A), purified alginate, an O-polysaccharide toxin A conjugate, or sterile saline. After challenge none of the rats immunized with D-ALG toxin A died, in contrast to the other two vaccine groups combined (p = 0.03). A significant reduction in the severity of the macroscopic lung inflammation was seen in rats immunized with D-ALG toxin A, compared with the other three groups (p = 0.009). The histopathologic response in the control rats was dominated by numerous polymorphonuclear leukocytes (PMN) surrounding the alginate beads. In contrast, the histopathologic response in rats immunized with D-ALG toxin A changed within the first week after challenge from predominantly PMNs (TH2-like) to a chronic-type inflammation dominated by mononuclear leukocytes (TH1-like). In accordance, the antibody titers induced by the D-ALG toxin A vaccine were not different from those of the control rats after challenge. This study identifies a possible new way of modifying the inflammation and thereby preventing the PMN-mediated lung tissue damage during chronic P. aeruginosa lung infection in CF.
| Original language | English |
|---|---|
| Journal | American Journal of Respiratory and Critical Care Medicine |
| Volume | 152 |
| Issue number | 4 Pt 1 |
| Pages (from-to) | 1337-46 |
| Number of pages | 10 |
| ISSN | 1073-449X |
| Publication status | Published - 1995 |
Keywords
- Alginates
- Animals
- Antibodies, Bacterial
- Bacterial Vaccines
- Cystic Fibrosis
- Disease Models, Animal
- Enzyme-Linked Immunosorbent Assay
- Female
- Leukocytes, Mononuclear
- Lung
- Neutrophils
- Pneumonia, Bacterial
- Pseudomonas Infections
- Pseudomonas aeruginosa
- Rats
- Rats, Inbred Lew
- Vaccination
