Lung defenses against viral and bacterial challenges during immunosuppression with cyclophosphamide in mice

G. J. Jakab, G. A. Warr

Research output: Contribution to journalArticlepeer-review

Abstract

Pulmonary virus infections predispose to secondary bacterial pneumonias by suppressing the antibacterial defenses of the lung. Cyclophosphamide (CY) treatment interferes with antiviral defenses and also impairs pulmonary bactericidal activity. To determine whether CY aggravates secondary bacterial pneumonias, mice were infected by aerosol inhalation with para-influenza 1 (Sendai) virus and injected intraperitoneally with either 0.5, 1.0, 2.5, or 5.0 mg of CY on Days 1 and 5 of the infection. On Day 7, the lungs of control (CY-treated but not infected) and virus-infected mice were lavaged and the total and differential number of free pulmonary cells quantitated. At the same time, other groups of mice were challenged aerogenically with Staphylococcus aureus and the number of initially viable bacteria remaining in their lungs quantitated at 4 and 24 h thereafter. The CY treatment induced a dose-dependent neutropenia, which was paralleled by the number of free pulmonary cells recovered from the lungs. Pulmonary bactericidal activity was also suppressed by CY treatment, with the percentage of staphylococci remaining at 24 h in the lungs of control animals being 0.5 ± 0.2% and 1.5 ± 0.5%, 4.0 ± 1.5%, 8.5 ± 2%, and 36 ± 5%, respectively, for the increasing doses of CY. In virus-infected animals, CY treatment suppressed the inflammatory response in a dose-dependent manner, with the total number of free lung cells recovered from the highest dose group being only 5% of that recovered from untreated animals. Virus infection depressed the antibactericidal defenses of the lung so that in untreated animals, 80 ± 9% of the staphylococci remained at 24 h. Treatment with the 2 higher doses of CY caused the bacteria to proliferate extensively in the lungs to 280 ± 53% and 792 ± 112%, respectively, for the 2.5 mg and 5.0 mg CY doses. In contrast, treatment with 0.5 mg and 1.0 mg of CY significantly enhanced the intrapulmonary killing of S. aureus in virus-infected lungs so that the bactericidal values at 24 h were 28 ± 3% and 21 ± 2%, respectively. These data demonstrated that immunosuppression modulates virus-induced suppression of pulmonary antibacterial defenses with high doses of CY aggravating and low doses ameliorating the defect.

Original languageEnglish (US)
Pages (from-to)524-528
Number of pages5
JournalAmerican Review of Respiratory Disease
Volume123
Issue number5
StatePublished - Jan 1 1981

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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