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MUCOSAL IL-12 IS MORE EFFECTIVE THAN SYSTEMIC IL-12 IN AUGMENTING IFN-γ EXPRESSION AND INHIBITING ALLERGIC LUNG EOSINOPHILIA IN MURINE LUNGS.
- Source :
-
Experimental Lung Research . Sep2000, Vol. 26 Issue 6, p457-476. 20p. 4 Black and White Photographs, 1 Diagram, 2 Charts, 11 Graphs. - Publication Year :
- 2000
-
Abstract
- The relative efficacy of mucosal (intratracheal) and systemic (intraperitoneal) delivery of interleukin (IL)-12 was evaluated in a mouse model of allergic lung eosinophilia. Mucosal administration of IL-12 achieved 100- to 600-fold higher bronchoalveolar lavage (BAL) levels of IL-12, but 2- to 10-fold lower serum levels compared to systemic administration. Whereas both mucosal and systemic IL-12 inhibited BAL eosinophil recruitment at high doses (100-1000ng), only mucosal IL-12 was effective at low doses (1-10ng). Mucosal, but not systemic, administration of 1000 ng of IL-12 increased interferon (IFN)-γ expression in BAL cells. In a model of ongoing eosinophilic inflammation, when mucosal or systemic IL-12 doses were initiated prior to peak eosinophilia, further eosinophil recruitment was inhibited. However, when IL-12 treatment was initiated after peak eosinophil recruitment occurred, recovery from eosinophilic inflammation was not facilitated. Our findings are the first to demonstrate that locally administered IL-12 inhibits eosinophil recruitment at 100-fold lower doses than systemic IL-12. The most likely mechanism of this enhanced inhibitory activity is a sustained increase in lung levels of IL-12 that augments IFN-γ production from BAL cells. We suggest that future studies should evaluate the efficacy of low doses of nebulized IL-12 in inhibiting eosinophilic lung inflammation in asthma. [ABSTRACT FROM AUTHOR]
- Subjects :
- *INTERLEUKIN-12
*ASTHMA treatment
*THERAPEUTICS
Subjects
Details
- Language :
- English
- ISSN :
- 01902148
- Volume :
- 26
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Experimental Lung Research
- Publication Type :
- Academic Journal
- Accession number :
- 3860799
- Full Text :
- https://doi.org/10.1080/01902140050130365