Local production of interleukin-4 during radiation-induced pneumonitis and pulmonary fibrosis in rats: macrophages as a prominent source of interleukin-4.
Fibrosis of lung tissue is a frequent and serious consequence of radiotherapy of mammary carcinoma. The pathogenesis of radiation-induced pulmonary fibrosis remains unclear. Cytokines such as transforming growth factor beta (TGFbeta) and interleukin-4 (IL-4) have been reported to stimulate collagen synthesis in fibroblasts in vitro. The aim of this study was to document the presence of IL-4 during the development of post-irradiation lung fibrosis. Right lungs of male Fischer rats were irradiated with a single dose of 20 Gy and IL-4 expression in the irradiated lungs was monitored for a period of three months. IL-4 gene transcription as determined by ribonuclease protection assay (RPA) as well as IL-4 synthesis as shown by Western blotting increased in the irradiated lungs reaching a plateau concentration within 3 weeks after irradiation. Enhanced IL-4 production was still detected at day 84 after irradiation. The cellular origin of IL-4 was analyzed by in situ hybridization and two-color immunofluorescence on lung tissue sections and on cytospin preparations of leukocytes obtained from bronchoalveolar lavages. These experiments revealed a substantial IL-4 production by macrophages during development of post-irradiation lung fibrosis.
Büttner
C
C
Institute of Immunology, Medical Faculty, Technical University Dresden, Germany. immunol@rcs.urz.tu-dresden.de
Skupin
A
A
Reimann
T
T
Rieber
E P
EP
Unteregger
G
G
Geyer
P
P
Frank
K H
KH
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression / Q000528:radiation effects; D017403:In Situ Hybridization; D015847:Interleukin-4 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015471:Leukemia, Basophilic, Acute; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D011658:Pulmonary Fibrosis / Q000209:etiology* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011832:Radiation Injuries / Q000150:complications; D017564:Radiation Pneumonitis / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000378:metabolism
D012333:RNA, Messenger; D015847:Interleukin-4