High doses of kefir accelerate lung-injury progression in bleomycin-induced pneumonitis in rats

Background: Bleomycin-induced pneumonitis (BIP) is a common consequence of bleomycin (BLE) use during chemotherapy. Kefir is a probiotic with many health benefits. Many cancer patients in Indonesia consume kefir as a complementary traditional medicine alongside standard chemotherapy. Objectives: This study aimed to investigate the effects of high-dose kefir consumption on BIP in a rat model. Methods: Wistar male rats were given 0.3 mg of BLE via intranasal inhalation for 6 days with a daily intragastric administration of either phosphate buffered saline (PBS) or kefir at dosages of 2.5 mL, 3.5 mL, and 4.5 mL per day for 30 days. On day 30, lung sections were obtained and stained with hematoxylin and eosin for histological examinations. Immunohistochemistry tests were carried out to determine the activity levels of matrix metalloproteinase (MMP)-1, signal transducer, and activator of transcription (STAT)-3. TNF-α and IL-6 concentrations in plasma were also evaluated. Results: Histological results showed damage to the lung structure by inflammation with diffuse infiltrate, with some areas exhibiting slight fibrosis. The number of alveolar epithelial cells expressing MMP-1 significantly increased with the kefir dosage. Interestingly, only the highest dose of kefir raised IL-6 levels, while TNF-α levels increased at all kefir doses. STAT-3 showed a slight increase in activity level. As MMP-1 works to degrade fibrosis while both TNF-α and Il-6 are correlated with inflammation, these findings might explain the observed histological changes in lung structure in the BLE and kefir groups. Conclusions: The administration of high doses of kefir in rats increased the expression of pro-inflammatory cytokines, which worsened BIP.