Vaccination promotes TH1-like inflammation and survival in chronic Pseudomonas aeruginosa pneumonia in rats

H K Johansen, H P Hougen, S J Cryz, J Rygaard, N Høiby

39 Citationer (Scopus)

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.
OriginalsprogEngelsk
TidsskriftAmerican Journal of Respiratory and Critical Care Medicine
Vol/bind152
Udgave nummer4 Pt 1
Sider (fra-til)1337-46
Antal sider10
ISSN1073-449X
StatusUdgivet - 1995

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