Effects of Adalimumab, an Anti-tumour Necrosis Factor-Alpha (TNF-α) Antibody, on Obese Diabetic Rats

Background: Diabetes mellitus (DM) represents a major health problem worldwide. Recent studies have confirmed that obesity is a state of chronic inflammation that is characterised by increased concentrations of tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and other inflammatory markers. It has been reported that increased TNF-α and IL-6 cause an immunological disturbance in DM. In the present study, the levels of fasting glucose, TNF-α and IL-6 were estimated in order to determine whether adalimumab can improve the glucose levels in obese diabetic rats.
Materials and methods: Twenty-eight Wistar rats were divided into four groups: obese + diabetes + adalimumab (group 1), obese + diabetes (group 2), obese (group 3) and normal control (group 4), respectively (n = seven per group). Obesity was induced by feeding the rats in groups 1, 2 and 3 with a high-fat diet for four weeks. Some 30 mg/kg of streptozotocin (STZ) was administered to groups 1 and 2 so as to induce diabetes. Adalimumab was administered at a rate of 50 mg/kg to group 1 following the induction of diabetes. The fasting glucose, TNF-α and IL-6 concentrations were determined.
Results: A significant decrease was observed in the glucose levels of the treated rats (6.91 [0.11] mmol/L) when compared to those of the untreated rats (15.43 [0.44] mmol/L) (P < 0.001). The TNF-α levels were lower in group 1 (20.71 [0.35] ng/L) than in groups 2 (37.90 [0.27] ng/L) and 3 (25.89 [0.12] ng/L) (P < 0.001), although they were higher when compared to the levels seen in group 4 (12.44 [0.38] ng/L) (P < 0.001). The IL-6 concentrations were found to be elevated in groups 1 (22.89 [0.45] ng/L), 2 (21.00 [0.40] ng/L) and 3 (31.80 [1.32] ng/L) when compared to the levels seen in group 4 (18.70 [0.37] ng/L) (P < 0.001), although they were lower in group 1 (22.89 [0.45] ng/L) than in group 3 (31.80 [1.32] ng/L) (P < 0.001).
Conclusion: Adalimumab reduced the glucose and TNF-α levels of diabetic rats, which indicates that it has a therapeutic effect in terms of controlling the blood glucose.