Effects of an antibody to interleukin-5 in a monkey model of asthma.
To investigate the role of interleukin-5 (IL-5) on airway hyperreactivity and pulmonary inflammation in nonhuman primate airways, the effect of a neutralizing monoclonal antibody to murine IL-5 (TRFK-5) was investigated in a cynomolgus monkey model of allergic asthma. Anesthetized Ascaris-sensitive monkeys underwent bronchoalveolar lavage (BAL) to assess the granulocyte content of this fluid before and 24 h after aerosolized Ascaris suum extract inhalation. Airway reactivity was assessed by the concentration of inhaled histamine required to produce a 40% reduction in dynamic lung compliance (Cdyn40). Exposure to A. suum extract produced an increase in airway reactivity (Cdyn40 = 0.065 +/- 0.024% before Ascaris; Cdyn40 = 0.014 +/- 0.004% after Ascaris) and an inflammatory reaction in the airways characterized by an increase in BAL eosinophils (0.05 +/- 0.03 x 10(3) cells/ml before Ascaris; 176 +/- 76 x 10(3) cells/ml after Ascaris) and neutrophils (3 +/- 1 x 10(3) cells/ml before Ascaris; 406 +/- 211 x 10(3) cells/ml after Ascaris). In contrast, only small nonsignificant changes in airway reactivity and granulocyte influx into the BAL occurred after aerosolized saline as a sham challenge. When the monkeys were treated 1 h before Ascaris challenge with the TRFK-5 antibody (0.3 mg/kg, intravenously), there was no increase in airway reactivity after Ascaris challenge (Cdyn40 = 0.032 +/- 0.016% before Ascaris; Cdyn40 = 0.217 +/- 0.196% after Ascaris) and there were only small increases in the number of eosinophils and neutrophils in the BAL after Ascaris challenge. The inhibition of this pulmonary eosinophilia and bronchial hyperresponsiveness by TRFK-5 was seen for up to 3 mo after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Mauser
P J
PJ
Department of Allergy, Schering-Plough Research Institute, Kenilworth, NJ 07033-0539, USA.
Pitman
A M
AM
Fernandez
X
X
Foran
S K
SK
Adams
G K
GK
Kreutner
W
W
Egan
R W
RW
Chapman
R W
RW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D017165:Ascaris suum; D001249:Asthma / Q000276:immunology* / Q000517:prevention & control; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000517:prevention & control; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology / Q000473:pathology; D006098:Granulocytes / Q000473:pathology; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology; D015848:Interleukin-5 / Q000276:immunology*; D007958:Leukocyte Count; D008170:Lung Compliance / Q000187:drug effects; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D009299:Nasal Provocation Tests; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D011014:Pneumonia / Q000276:immunology / Q000517:prevention & control; D011657:Pulmonary Eosinophilia / Q000276:immunology / Q000517:prevention & control; D012123:Pulmonary Ventilation / Q000187:drug effects
D000911:Antibodies, Monoclonal; D015848:Interleukin-5; D006632:Histamine