Inhaled recombinant interferon gamma in patients with lung cancer: pharmacokinetics and effects on chemiluminescence responses of alveolar macrophages and peripheral blood neutrophils and monocytes. International journal of radiation oncology, biology, physics. [Int J Radiat Oncol Biol Phys] Journal article | | Title | Inhaled recombinant interferon gamma in patients with lung cancer: pharmacokinetics and effects on chemiluminescence responses of alveolar macrophages and peripheral blood neutrophils and monocytes. | | Author(s) | Halme M, Maasilta P, Repo H, Ristola M, Taskinen E, Mattson K, Cantell K | | Institution | Department of Pulmonary Medicine, Helsinki University Central Hospital, Finland. | | Source | Int J Radiat Oncol Biol Phys 1995 Jan 1; 31(1):93-101. | | MeSH | Adult
Aerosols
Aged
Bronchoalveolar Lavage Fluid
Carcinoma, Non-Small-Cell Lung
Carcinoma, Small Cell
Chemiluminescent Measurements
Female
Humans
Interferon-gamma, Recombinant
Lung Neoplasms
Macrophage Activation
Macrophages, Alveolar
Male
Middle Aged
Monocytes
Neutrophils
Reactive Oxygen Species
Research Support, Non-U.S. Gov't
Respiratory Burst
Time Factors
| | Abstract | PURPOSE: A Phase I trial was conducted to investigate clinical toxicity, pharmacokinetics, and chemiluminescence (CL) responses of alveolar macrophages (AM) and peripheral blood neutrophils and monocytes after inhalation of recombinant interferon (r IFN)-gamma.
METHODS AND MATERIALS: Eight patients with lung cancer inhaled r IFN-gamma as single doses of 0.1, 0.2, 0.6, 1.8, or 5.4 mg. Bronchoalveolar lavage was performed three times, 21 h before as well as 3 and 27 h after inhalation.
RESULTS: Interferon-gamma was detectable in bronchoalveolar lavage fluid (BALF) samples taken 3 h after inhalation in doses of > or = 0.6 mg. Before inhalation, AM in four out of seven patients studied showed vigorous lucigenin-enhanced CL responses to N-formyl-methionyl-leucyl-phenylalanine and opsonized zymosan particles. Furthermore, the responses were markedly increased 3 h after inhalation. In three out of seven patients, AM in the pretreatment BALF samples showed low or no CL responses, and the responses did not increase after inhalation of IFN-gamma, suggesting that the patients were anergic. Postinhalation CL responses did not correlate with the dose of IFN-gamma inhaled. Circulating IFN-gamma was detected in one patient receiving the highest dose. No changes referable to IFN-gamma inhalation were found in the CL responses of blood neutrophils and monocytes. During the 24 h follow-up, two patients developed transient fever-reactions.
CONCLUSIONS: The findings suggest that inhalation may provide a way to increase alveolar concentrations of IFN-gamma and to augment respiratory burst capacity of AM without any major side effects. This approach may have clinical implications for the treatment of tumors and infections of the respiratory tract. | | Language | eng | | Pub Type(s) | Clinical Trial
Controlled Clinical Trial
Journal Article
| | PubMed ID | 7995773 |
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