Since both vaccines have previously evoked high Bafetinib titers of IgG antibodies against alginate, LPS, and toxin A in healthy volunteers, an immunologic interference may have occurred in the rats, resulting in an antagonistic antibody response. The reason for this is unclear but may be related to immunosuppressive effects of some P. aeruginosa LPSs. Toxin A is known to be an important virulence factor, and when it is secreted by P. aeruginosa, it has been shown to be associated with severe bronchial inflammation and parenchymal changes. Anti toxin A antibodies could be demonstrated in all rats immunized with toxin A conjugated vaccines. However, toxin A did not significantly improve the lung abnormalities when compared with the sterile saline controls.
The protective capability of the LPS vaccine used in the present study is not completely in accordance with the findings of Pennington et al. We found that rats immunized with LPS containing P. aeruginosa sonicate had more severe lung damage and reduced Epothilone B bacterial elimination but had higher antibody titers directed against most of the antigens used in the ELISAs. The severe abnormalities and reduced clearance could be due to hypersensitivity reactions, e. g, immune complexes, of which there was no evidence in the study performed by Pennington et al. The more severe macroscopic abnormalities observed among our immunized rats fit well with the observations of Langford and Hiller, who found that vaccination of noninfected CF patients with a polyvalent P. aeruginosa vaccine induced more rapid deterioration than that found in nonvaccinated controls.
The accelerated course of the disease in vaccinated patients may also be explained by hypersensitivity reactions, e. g, immune complex mediated lung tissue damage, which occurs during chronic lung infection in CF. In conclusion, this study shows that none of the vaccines used could completely prevent chronic lung inflammation 4 weeks after challenge with P. aeruginosa containing alginate beads. In all immunized rats and the IFA control group, we succeeded in changing the inflammatory response from an acute type inflammation dominated by PMN leukocytes as in CF patients to a chronic type inflammation dominated by mononuclear leukocytes.
The altered abnormalities in immunized rats and the improved bacterial clearance might be of great advantage in future management of CF patients, since the ongoing lung tissue damage has been shown to be caused by elastase secreted by PMNs, which dominate the chronic P. aeruginosa lung infection in CF patients. ACKNOWLEDGMENTS The expert technical assistance of Ellen Frederiksen and Jette Pedersen is greatly appreciated. This study was supported by grants from the King Christian IX and Queen Louise Jubilee Foundation, Danish Hospital Foundation for Medical Research of Copenhagen, The Faroe Islands and Greenland grants 54/91, 47/92 and 48/93, Director Jacob Madsen and Olga Madsen,s Foundation grants 2029/1992 and 2272/1993, Ville Heises Foundation grant 5/92, the King Christian X Foundation, and Queen Louise Research Foundation grant 8/92. Abstract Objective Central pain augmentation resulting from enhanced excitatory and/or decreased inhibitory neurotransmission is a proposed mechanism underlying the pathophysiology of f