Effects of interleukin 5-induced pulmonary eosinophilia on airway reactivity in the guinea pig.
Administration of interleukin 5 (IL-5) to guinea pigs by tracheal injection was associated with increased recovery of eosinophils and neutrophils from bronchoalveolar lavage (BAL) fluid. The number of eosinophils recovered from BAL fluid increased in a dose-dependent manner from 9 +/- 2 X 10(3)/ml to a plateau of 143 +/- 29 X 10(3)/ml after the administration of recombinant human IL-5 (rhIL-5). Tracheal administration of recombinant guinea pig IL-5 (gpIL-5) also increased eosinophil recovery but was less potent than rhIL-5. Histological analysis confirmed the presence of inflammatory cells in the lung; there were higher grades of inflammation in airway than in parenchymal tissue after gpIL-5 administration. In addition, the histological grade of airway inflammation was greater 24 and 72 h after gpIL-5 administration than it was 6 days after administration. Airway hyperresponsiveness is reported to occur in guinea pigs exposed to rhIL-5 by intraperitoneal cellular production. It is surprising that airway infiltration with eosinophils induced by the topical application of IL-5 was not associated with hyperresponsiveness to substance P, histamine, or platelet-activating factor in intact animals or to methacholine in tracheally perfused lungs. Furthermore, the microvascular leakage induced by substance P was not altered by rhIL-5 administration. These findings indicate that the presence of eosinophils alone is not sufficient for the expression of airway hyperresponsiveness. Our ability to separate eosinophil recruitment and retention in the tissues from airway hyperresponsiveness indicates that these two processes are distinct and that the presence of eosinophils in lung tissue, by itself, is not sufficient to alter airway contractile responses.
Lilly
C M
CM
Department of Medicine, Brigham and Womens Hospital, Boston, Massachusetts 02115, USA.
Chapman
R W
RW
Sehring
S J
SJ
Mauser
P J
PJ
Egan
R W
RW
Drazen
J M
JM
D000818:Animals; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D006801:Humans; D015848:Interleukin-5 / Q000494:pharmacology*; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D010477:Perfusion; D011994:Recombinant Proteins / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000502:physiology*
D015848:Interleukin-5; D011994:Recombinant Proteins