Effects of IL-4 on pulmonary fibrosis and the accumulation and phenotype of macrophage subpopulations following thoracic irradiation

Abstract

Purpose: Thoracic irradiation injures lung parenchyma, triggering inflammation and immune cell activation, leading to pneumonitis and fibrosis. Macrophage polarization contributes to these processes. Since IL-4 promotes pro-fibrotic macrophage activation, its role in radiation-induced lung injury was investigated.

Materials and methods: Lung macrophage subpopulations were characterized from 3–26 weeks following exposure of WT and IL-4−/− mice to 0 or 12.5 Gray single dose thoracic irradiation.

Results: Loss of IL-4 did not prevent fibrosis, but blunted macrophage accumulation within the parenchyma. At 3 weeks following exposure, cell numbers and expression of F4/80 and CD206, an alternative activation marker, decreased in alveolar macrophages but increased in infiltrating macrophages in WT mice. Loss of IL-4 impaired recovery of these markers in alveolar macrophages and blunted expansion of these populations in infiltrating macrophages. CD206+ cells were evident in fibrotic regions of WT mice only, however Arg-1+ cells increased in fibrotic regions in IL-4−/− mice only. Radiation-induced proinflammatory Ly6C expression was more apparent in alveolar and interstitial macrophages from IL-4−/− mice.

Conclusions: IL-4 loss did not prevent alternative macrophage activation and fibrosis in irradiated mice. Instead, a role is indicated for IL-4 in maintenance of macrophage populations in the lung following high single dose thoracic irradiation.

Keywords:

• IL-4
• macrophage
• pulmonary fibrosis
• radiation

Disclosure statement

The authors report no conflicts of interest. The authors alone are response for the content and writing of the paper.

Funding

National Heart Lung and Blood Institute,10.13039/100000050 [ES T32 07026]; National Institute of Allergy and Infectious Diseases, 10.13039/100000060 [R01 AI101732-01, U19AI091036]; National Institute of Environmental Health Sciences, 10.13039/100000066 [P30 ES-01247].