Mucosal IL-12 is more effective than systemic IL-12 in augmenting IFN-gamma expression and inhibiting allergic lung eosinophilia in murine lungs.

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 (100-1000 ng), only mucosal IL-12 was effective at low doses (1-10 ng). Mucosal, but not systemic, administration of 1000 ng of IL-12 increased interferon (IFN)-gamma 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-gamma 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.

• Authors: S Sur, B K Choudhury, J S Lam, P Bouchard, J S Wild, N Sur, R Alam, A Sigounas, D Holbert, M R Van Scott
• Journal: Experimental lung research (Exp Lung Res) Vol. 26 Issue 6 Pg. 457-76 (Sep 2000) ISSN: 0190-2148 [Print] England
• PMID: 11033768 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Adjuvants, Immunologic
• Allergens
• RNA, Messenger
• Interleukin-12
• Interferon-gamma

Topics

• Adjuvants, Immunologic (administration & dosage, blood)
• Allergens (immunology)
• Animals
• Asthma
• Bronchoalveolar Lavage Fluid (chemistry, cytology)
• Disease Models, Animal
• Injections, Intraperitoneal
• Interferon-gamma (biosynthesis, genetics)
• Interleukin-12 (administration & dosage, blood)
• Intubation, Intratracheal
• Lung (drug effects, pathology)
• Mice
• Mice, Inbred BALB C
• Pollen (immunology)
• Pulmonary Eosinophilia (immunology, pathology, prevention & control)
• RNA, Messenger (metabolism)
• Respiratory Mucosa (drug effects)
• Reverse Transcriptase Polymerase Chain Reaction