AZD8931 due to hypersensitivity reactions

This severity could be AZD8931 due to hypersensitivity reactions, e. g, immune complex mediated lung tissue damage as in CF. When these results were compared with previous findings in nonvaccinated rats, the only group which persistently showed similar histopathologic findings was the control group receiving sterile saline. In these rats 4 weeks after challenge, PMNs surrounded the alginate beads containing the bacteria as in CF. With regard to changing the inflammatory response, the effect caused by the P. aeruginosa containing vaccines was equal to that in rats injected with IFA, since the inflammatory response in these rats also changed to a chronic type inflammation with mononuclear leukocytes and eradication of most of the bacteria. The vaccine induced antibodies therefore seem to play a minor role in prevention of the inflammation.
This shift from an acute to a chronic inflammation is potentially very important since the tissue damage in CF has been shown by many authors to be caused by PMN elastase. There is a considerable body of evidence that adjuvants can influence the antibody isotype and cell mediated immunity in rodents. MGCD-265 All the P. aeruginosa vaccines in the present study were adsorbed to either Al3 or IFA. These two adjuvants both enhance the IgGl antibody response and induce Thl VOL. 62, 1994 3152 JOHANSEN ET AL. FIG. 1. Photomicrograph of a section from the lower portion of the left lung in a normal rat injected with sterile saline 28 days after challenge with 109 CFU of P. aeruginosa containing alginate beads per ml. Note the dense accumulation of PMNs surrounding the alginate bead with P.
aeruginosa bacteria located as microcolonies within the bead as in CF patients. Stain, hematoxylin and eosin. Magnification, x 1,000. Photomicrograph of a section from the lower portion of the left lung in a normal rat immunized with D ALG toxin A conjugate 28 days after challenge with 109 CFU of P. aeruginosa containing alginate beads per ml. Note the alginate bead surrounded by mononuclear leukocytes, different from the situation observed in CF patients. Stain, hematoxylin and eosin. Magnification, x 1,000. lymphocytes, and they should therefore induce similar pathologic and serologic effects in the vaccine groups.
The adjuvant effect caused by IFA is in accordance with previous findings by Roberts et al, who found that injection with complete Freund,s adjuvant reduced the severity of an acute pneumonia caused by Streptococcus pneumoniae in rat lungs when compared with that in rats not receiving CFA. Buhles et al. found that immune stimulation of granulocytopenic mice with CFA partially protected them against the lethal consequences of subsequent infection with Staphylococcus aureus. The tendencies in our experiment with IFA and the two experiments with CFA are similar. However, CFA includes mycobacteria in the oil and therefore possesses even stronger immunomodulatory traits than IFA INFECT. IMMUN. IMMUNIZATION WITH P. AERUGINOSA VACCINES 3153 since it also leads to the appearance of IgG2 antibodies and to a delayed hypersensitivity reaction. The slight increase in IgM, IgG, and IgA antibodies to, e. g, alginate in the control animals injected with NaCl or especially IFA correlates with the older age of the animals, which is known to l