Ameliorating effect of erythromycin on bleomycin-induced pulmonary fibrosis: role of alveolar macrophage activation and cytokine release.
The objective of this study was to evaluate the effectiveness of erythromycin (EM) on bleomycin-induced pulmonary fibrosis in rats and its possible mechanisms. Seventy-five rats were divided into three groups. Alveolar macrophages (AM) were harvested through bronchalveolar lavage (BAL) and consecutive changes of tumour necrosis factor-alpha (TNF-alpha) and platelet-derived growth factor (PDGF) in AM supernatant and bronchoalveolar lavage fluid (BALF) were assayed with ELISA and bioassay, respectively. The AM-derived TNF-alpha was elevated on day 3, peaked day 7 and then decreased but remained at higher level until day 28. The AM-derived PDGF was increased on day 3, peaked on day 7 then decreased to non-statistically significant higher level. The TNF-alpha in BALF was increased significantly on day 3 then decreased to normal level; the peak preceded that of AM-derived TNF-alpha. The PDGF in BALF was increased on day 3, peaked on day 7, and then decreased to normal, which exhibited a consecutive change similar to that of AM-derived PDGF. The EM significantly suppressed TNF-alpha and PDGF release by AM, markedly decreased TNF-alpha and PDGF levels in BALF. The EM also lessened the collagen deposition, the lung hydroxyproline comprised 75.44%, 72.72% and 56.24% that of bleomycin-treated group on day 7, 14 and 28, respectively. In conclusion, EM can ameliorate bleomycin-induced pulmonary fibrosis possibly through suppression of TNF-alpha and PDGF as well as the inhibition on accumulation of inflammatory cells in the lung.
Chen
B
B
Institute of Respiratory Disease, China Medical University, Shenyang, China.
Jiang
L
L
Zhao
W
W
Yu
R
R
Hou
X M
XM
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D004917:Erythromycin / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006909:Hydroxyproline / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008262:Macrophage Activation / Q000187:drug effects*; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000187:drug effects* / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects* / Q000378:metabolism
D000900:Anti-Bacterial Agents; D016207:Cytokines; D010982:Platelet-Derived Growth Factor; D014409:Tumor Necrosis Factor-alpha; D001761:Bleomycin; D004917:Erythromycin; D006909:Hydroxyproline