Modulation of Altered Immune Parameters IL-2 and TNF-α in Diabetic Animal Models: A Therapeutic Insinuation of Metformin Beyond Diabetes.

Abstract

Immunomodulatory drugs target the overall immune system, hence producing numerous toxic effects on the other organs with serious health manifestations. Due to these safety concerns, there is aneed to introduce or repurpose a new drug with immunomodulatory effects with good safety, efficacy, and better tolerance. Metformin, a standard antidiabetic drug, was evaluated for its immunomodulatory effects in diabetic models in the current study. The diabetic model was developed by intraperitoneal (IP) administration of streptozotocin (60 mg/kg). The experimental rats were divided into six groups (three diabetic and three non-diabetic) with six rats in each group. Metformin (50 mg/kg and 80 mg/kg) was given orally to both diabetic and non-diabetic groups, once a day, for 42 days. Immunomodulatory cytokinesinterleukin (IL)-2, IL-4, IL-5, tumor necrosis factor (TNF)-α, and interferon gamma (INF-ɣ)were analyzed from blood samples by BD FCAP flow cytometer. The results revealed a significant (p=0.002) decrease in IL-2 and TNF-α in diabetic groups in comparison to control rats. However, no significant changes were observed in IL-4, IL-5, and INF-ɣ levels. Importantly, the treatment of metformin at both doses, i.e., 50 and 80 mg/kg, significantly reduced the elevated levels of IL-2 and TNF-α when compared to untreated diabetic groups. Metformin may be considered as an optimum drug candidate to reduce pro-inflammatory cytokines, IL-2 and TNF-α, that can lead to the reduction of long-term diabetic complications.