| Title | The effects of inhaled interferon gamma in normal human airways. | | Author(s) | Martin RJ, Boguniewicz M, Henson JE, Celniker AC, Williams M, Giorno RC, Leung DY | | Institution | Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206. | | Source | Am Rev Respir Dis 1993 Dec; 148(6 Pt 1):1677-82. | | MeSH | Administration, Inhalation
Adult
Aerosols
Bronchi
Bronchial Provocation Tests
Bronchoalveolar Lavage Fluid
Chemokines, CXC
Cytokines
Humans
Interferon-gamma, Recombinant
Interleukin-1
Interleukin-8
Macrophage Activation
Macrophages, Alveolar
Male
Methacholine Chloride
Peak Expiratory Flow Rate
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Respiratory Physiology
Respiratory System
Transcription, Genetic
| | Abstract | Recent studies suggest that cytokines such as recombinant interferon-gamma (rIFN-gamma) may play a role in the treatment of certain respiratory conditions associated with infection and inflammation. This study was designed to determine if rIFN-gamma could be delivered effectively in a group of normal human volunteers. The effectiveness of the inhaled delivery system was demonstrated by the recovery of free IFN-gamma in bronchoalveolar lavage (BAL) fluid and macrophage (M phi) expression of IP-10, an IFN-gamma-inducible molecule, after therapy but not at baseline. IL-1 beta, but not IL-8, gene transcripts also showed evidence for up-regulation after rIFN-gamma therapy. Compared with baseline, inhaled rIFN-gamma did not significantly alter clinical symptom scores, spirometry, morning peak expiratory flow rate (PEFR), or the response to methacholine. Of interest, the evening PEFR increased significantly (p = 0.02), from 568 +/- 36 L/min at baseline to 584 +/- 33 L/min after inhaled rIFN-gamma. Although there was no significant change in total white cell count in BAL fluid, the cellular composition did demonstrate a significant decrease in percentage of alveolar M phi (p = 0.02) and an increase in percentage of lymphocytes (p = 0.02) after rIFN-gamma. There were no histologic differences seen in bronchial biopsy specimens, and there was no evidence for up-regulation of ICAM-1 or HLA-DR expression after rIFN-gamma. We conclude that, in normal persons, rIFN-gamma can be effectively delivered by inhalation. Future trials using inhaled rIFN-gamma appear to be warranted for certain pulmonary diseases. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 8256919 |
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