Recombinant interleukin-5 induces in vivo airway hyperresponsiveness to histamine in guinea pigs.
Interleukin-5-producing CV-1 cells were encapsulated in alginate and injected i.p. in guinea pigs (4 x 10(6)/animal). These cells produced approximately 8 ng interleukin-5 per 4 x 10(6) cells per day. Airway hyperresponsiveness to histamine in vivo was observed 3 and 7 days after administration. The increase in lung resistance after intravenous administration of histamine to guinea pigs was significantly potentiated, by approximately 70 to 90% in interleukin-5-treated animals. In animals treated with antibody to interleukin-5, the administration of interleukin-5-producing CV-1 cells did not induce hyperresponsiveness. The percentage of eosinophils in broncho-alveolar lavage fluid was increased by 100% at 7 days but not at 3 days after administration of interleukin-5-producing CV-1 cells. Antibody to interleukin-5 prevented the broncho-alveolar lavage eosinophilia at 7 days after interleukin-5 administration. It can be concluded that interleukin-5 induces broncho-alveolar lavage eosinophilia and airway hyperresponsiveness and that these phenomena do not occur simultaneously. These data suggest a role for interleukin-5 in the development of airway hyperresponsiveness in bronchial asthma.
Van Oosterhout
A J
AJ
Department of Pharmacology, Faculty of Pharmacy, Utrecht University, Netherlands.
Van Ark
I
I
Hofman
G
G
Savelkoul
H F
HF
Nijkamp
F P
FP
D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D000911:Antibodies, Monoclonal; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D002452:Cell Count; D002460:Cell Line; D004804:Eosinophils / Q000187:drug effects*; D006168:Guinea Pigs; D000882:Haplorhini; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D015848:Interleukin-5 / Q000276:immunology / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D014162:Transfection
D000911:Antibodies, Monoclonal; D015848:Interleukin-5; D011994:Recombinant Proteins; D006632:Histamine