Effect of anti-IL-5 and IL-5 on airway hyperreactivity and eosinophils in guinea pigs.
Chronic ovalbumin challenge of sensitized guinea pigs induces bronchoalveolar lavage (BAL) eosinophilia, neutrophilia, and tracheal hyperreactivity. In the present study, the influence of monoclonal antibody to murine interleukin-5 (anti-IL-5) on these phenomena is examined. In ovalbumin-sensitized guinea pigs treated with isotype-matched control antibody and challenged daily with ovalbumin for 8 days, the number of BAL eosinophils and neutrophils is increased significantly six- and fivefold, respectively, compared with saline-challenged animals. The maximal contractions of tracheal rings to histamine and arecoline in ovalbumin-challenged animals are enhanced significantly to 155% compared with saline-challenged animals. In sensitized guinea pigs treated with anti-IL-5, the BAL eosinophil number is markedly inhibited compared with control antibody treatment in both saline- and ovalbumin-challenged animals. In contrast, the number of neutrophils is not affected by anti-IL-5 treatment. In guinea pigs treated with anti-IL-5, the development of hyperreactivity to histamine and arecoline after ovalbumin challenge is completely inhibited. The contractions to histamine and arecoline of tracheal rings isolated from guinea pigs treated with recombinant murine IL-5 for 3 or 7 days are enhanced significantly to approximately 140% compared with controls. Treatment with IL-5 for 7 days tends to increase the number of eosinophils in BAL fluid. It can be concluded that IL-5 is involved in airway eosinophilia and in the development of hyperreactivity in this animal model, but other cytokines may contribute. Development of IL-5 synthesis inhibitors and/or receptor antagonists could provide another therapeutic class of anti-asthma drugs.
Van Oosterhout
A J
AJ
Department of Pharmacology, Faculty of Pharmacy, Utrecht University, The Netherlands.
Ladenius
A R
AR
Savelkoul
H F
HF
Van Ark
I
I
Delsman
K C
KC
Nijkamp
F P
FP
D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000302:isolation & purification / Q000494:pharmacology*; D001115:Arecoline / Q000494:pharmacology; D016535:Bronchial Hyperreactivity / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004802:Eosinophilia / Q000453:epidemiology / Q000209:etiology / Q000276:immunology; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006825:Hybridomas / Q000276:immunology; D007114:Immunization; D007132:Immunoglobulin Isotypes / Q000494:pharmacology; D015848:Interleukin-5 / Q000276:immunology* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D013047:Specific Pathogen-Free Organisms; D014132:Trachea / Q000166:cytology / Q000187:drug effects
D000911:Antibodies, Monoclonal; D007132:Immunoglobulin Isotypes; D015848:Interleukin-5; D011994:Recombinant Proteins; D001115:Arecoline; D006632:Histamine; D010047:Ovalbumin