Rapid and selective induction of blood eosinophilia in guinea pigs by recombinant human interleukin 5.
Interleukin 5 (IL-5) has been implicated as a causal mediator in the development of pulmonary eosinophilia and airway hyperreactivity in human asthma. Supportive evidence for a pathogenic role of IL-5 in this disease has been provided by guinea pig models in which antigen-induced lung eosinophilia and bronchial hyperresponsiveness have been specifically attenuated with a neutralizing antibody to IL-5. In the present report, we describe a rapid mechanism-based model of IL-5-induced eosinophilia in the guinea pig. Our results show that intravenous injection of human IL-5 induced a 5-10-fold increase in the percentage and number of eosinophils in blood within 1 hour. In contrast, neutrophils and mononuclear cells were not recruited during this time. The increase in eosinophils was blocked by pretreatment of animals with an anti-IL5 monoclonal antibody (TRFK5) in doses similar to those which inhibit eosinophilia in guinea pig asthma models. Furthermore, dexamethasone, a potent inhibitor of eosinophilia in guinea pig asthma, profoundly suppressed the eosinophilia induced by human IL-5. This rapid model will be useful for elucidating the eosinophil activating properties of IL-5 in vivo and may potentially facilitate the development of IL-5 receptor antagonists for the specific blockade of the eosinophilic inflammation observed in human asthma.
Portanova
J P
JP
Department of Immunoinflammatory Diseases Research, G.D. Searle & Co. R&D, St. Louis, MO 63198, USA.
Christine
L J
LJ
Rangwala
S H
SH
Compton
R P
RP
Hirsch
J L
JL
Smith
W G
WG
Monahan
J B
JB
D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D004802:Eosinophilia / Q000139:chemically induced* / Q000276:immunology / Q000517:prevention & control; D006168:Guinea Pigs; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007275:Injections, Intravenous; D015848:Interleukin-5 / Q000008:administration & dosage / Q000276:immunology; D007700:Kinetics; D008297:Male; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D015848:Interleukin-5; D011994:Recombinant Proteins