Effect of ICAM-1 blockade on lung inflammation and physiology during acuteviral bronchiolitis in rats

Viral respiratory infections cause acute bronchiolitis and physiologic dysf unction in human infants and in animals. It is possible that the pulmonary dysfunction is a consequence of the inflammatory cells that are recruited d uring viral illness. We hypothesized that blockade of intercellular adhesio n molecule-1 (ICAM-1), a major cell adhesion molecule, would impede the ing ress of leukocytes during viral infection and attenuate virus-induced pulmo nary dysfunction. Adult male rats were inoculated with parainfluenza type 1 (Sendai) virus or sterile vehicle, and treated with blocking or nonblockin g MAb specific for rat ICAM-1. Respiratory system resistance, oxygenation ( Pao(2)), methacholine responsiveness, and bronchoalveolar lavage (BAL) leuk ocyte counts were measured in anesthetized, paralyzed, ventilated rats. Tre atment with the blocking ICAM-1 antibody reduced virus-induced increases in BAL neutrophils and lymphocytes by 70% (p < 0.001), but did not affect BAL monocytes/macrophages. Peripheral blood leukocyte counts were elevated in anti-ICAM-1 blocking antibody-treated rats (p = 0.0003). Although virus-ind uced increases in resistance and decreases in Pao(2) were not affected by a nti-ICAM-1 treatment, there was a small but significant attenuation of viru s-induced methacholine hyperresponsiveness (p = 0.02). We conclude that ICA M-1 has an important role in neutrophil and lymphocyte infiltration during respiratory viral illness, and that virus-induced changes in pulmonary phys iology are not related directly to the numbers of neutrophils and lymphocyt es that migrate to the air spaces during infection.