The effects of inhaled interferon gamma in normal human airways.
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.
Martin
R J
RJ
Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Boguniewicz
M
M
Henson
J E
JE
Celniker
A C
AC
Williams
M
M
Giorno
R C
RC
Leung
D Y
DY
D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols; D001980:Bronchi / Q000166:cytology; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D016207:Cytokines / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D016210:Methacholine Chloride; D010366:Peak Expiratory Flow Rate; D011994:Recombinant Proteins; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System / Q000166:cytology* / Q000378:metabolism; D014158:Transcription, Genetic
D000336:Aerosols; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D016207:Cytokines; D007375:Interleukin-1; D016209:Interleukin-8; D011994:Recombinant Proteins; D016210:Methacholine Chloride; D007371:Interferon-gamma