EFFECTS OF METFORMIN ON TNF-α RELEASE IN LIPOPOLYSACCHARIDE-INDUCED MONOCYTES IN RATS

Inflammation which is a response of immune system was demonstrated in many disorders such as atherosclerosis, hypertension, diabetes, cancer and rheumatoid arthritis. Metformin, an oral antidiabetic drug, has anti-inflammatory effect apart from blood glucose regulatory effect. However, the mechanism of its anti-inflammatory effect is not clearly understood. In this study, the effect of metformin on the release of cytokines (TNF-α and IL-6) from LPS stimulated rat mononuclear blood cells was investigated. Blood samples (5ml) were taken from healthy, male, 8-12 weeks old rats (n=5, 200-250g) through cardiac puncture under general anesthesia into sterile EDTA containing tubes. Monocytes were separated by centrifugation and were resuspended in RPMI 1640 media (3.3±0.2x105 /ml). Cells were then incubated with metformin (2.5 µM, 25 µM, 250 µM) for 2,5 hours followed by addition of LPS (100 ng/ml, 1µg/ml) for further 5 hours. After centrifugation, the supernatant was taken and TNF-α level was measured by ELISA. There was no statistically significant change in the amounts of TNF-α in the LPS + metformin groups compared to the 100 ng/ml LPS group (p>0.05). In LPS+metformin groups, compared to 1 µg/ml LPS, 2.5 µM and 250 µM metformin significantly increased TNF-α levels (p0.05). The amount of IL-6 was not within measurable range in this study. In summary, metformin increased the amount of released TNF-α rather than decreased in our study.