Anti-interleukin (IL)-4 and -IL-5 antibodies downregulate IgE and eosinophilia in mice exposed to Aspergillus antigens.
The effect of multiple divided doses compared with single-dose injections of antibodies to murine interleukin (IL)-4 and IL-5 in their respective downregulation of IgE and eosinophilia developing in a model of allergic aspergillosis is investigated. BALB/c mice were exposed to Aspergillus fumigatus antigens (Af) before and along with anticytokine antibodies. The kinetics of blood eosinophils, eosinophil peroxidase (EPO) in bone-marrow cells, serum levels of IgE and Af-specific antibodies, Af-induced cytokine production and mRNA, and lung histology were studied. The results indicate that only multiple anti-IL-5 antibodies were effective in maintaining baseline levels of blood eosinophils. Multiple anti-IL-4 antibodies also downregulated eosinophils in the bone marrow, lung, and peripheral blood, although to a lesser extent than in anti-IL-5 antibody-injected mice. Significant correlation between the EPO activity and the eosinophil numbers in anticytokine antibody-treated mice was observed. The different anti-IL-4 antibody treatments downregulated IgE to the same extent. We conclude that multiple divided doses of anti-IL-5 antibodies are required to sustain normal eosinophil levels in murine allergic aspergillosis. This information may be significant in the therapy of pulmonary allergic diseases.
Kurup
V P
VP
Department of Medicine, Medical College of Wisconsin, Milwaukee, USA.
Murali
P S
PS
Guo
J
J
Choi
H
H
Banerjee
B
B
Fink
J N
JN
Coffman
R L
RL
D000818:Animals; D000908:Antibodies, Fungal / Q000032:analysis; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D001232:Aspergillus fumigatus / Q000235:genetics / Q000276:immunology; D001853:Bone Marrow / Q000201:enzymology; D015536:Down-Regulation; D047209:Eosinophil Peroxidase; D004802:Eosinophilia / Q000276:immunology*; D004804:Eosinophils / Q000201:enzymology / Q000473:pathology; D007073:Immunoglobulin E / Q000097:blood*; D007074:Immunoglobulin G / Q000097:blood; D015847:Interleukin-4 / Q000276:immunology*; D015848:Interleukin-5 / Q000276:immunology*; D007958:Leukocyte Count; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010544:Peroxidases / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D013154:Spleen / Q000737:chemistry
D000908:Antibodies, Fungal; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D015848:Interleukin-5; D012333:RNA, Messenger; D015847:Interleukin-4; D007073:Immunoglobulin E; D047209:Eosinophil Peroxidase; D010544:Peroxidases