Elevated T-helper 2 cytokine levels in high fat diet-fed C57BL/6 mice are attenuated by short-term 6-week treatment with a combination of low-dose aspirin and metformin.

OBJECTIVE

To evaluate T-helper cytokine responses in a short-term high fat diet (HFD) induced impaired glucose metabolism. To further evaluate the modulation of T-helper 1 (Th) and T-helper 2 (Th) cytokines using short-term low-dose aspirin in combination with metformin.

DESIGN

Two experiments were carried out in this study in order to evaluate the T-helper cytokine profiles in a state of impaired glucose metabolism. A total of 28 six-week-old male C57BL/6 mice were used in this study. In the first experiment, mice were fed either a high fat diet or low fat diet for a duration of 10 weeks. We then determined the Th, Th and T-helper 17 (Th) cytokine profiles. In the second experiment, we evaluated whether the short term 6-week treatment with low-dose aspirin in combination with metformin modulates T-helper cytokine profiles of the HFD-fed mice.

MEASUREMENTS

In the first experiment, we measured the body weights, blood glucose levels, insulin levels, lipid profiles and haematological parameters. We further performed oral glucose tolerance testing following an 8-hour fast and serum Th, Th and Th cytokine levels were also determined following short-term 8-week diet-feeding and 6-week low-dose aspirin and combined metformin with low-dose aspirin treatment.

RESULTS

High fat diet-feeding caused a marked increase in circulating peripheral blood lymphocytes, which was attenuated by short-term low-dose aspirin treatment. Moreover, the HFD feeding resulted in 2-fold increase in total cholesterol and a 4-fold increase in low-density lipoprotein cholesterol when compared to the low-fat diet-fed group (p < 0.05). In the high fat diet group, impaired glucose metabolism was associated with skewed Th responses without alterations in the Th and Th cytokine profiles. Interestingly the short-term treatment with low-dose aspirin showed no effect on the selected T-helper 1 cytokine IFN-Ƴ (P > 0.05). While the combination of low-dose aspirin with metformin considerably reduced the levels of serum IFN-Ƴ (P < 0.05). Furthermore low-dose aspirin treatment showed the modest attenuation of the selected Th cytokines, IL-10 and IL-13 when compared to low-dose aspirin with metformin (P < 0.01).

CONCLUSION

The early immunological and metabolic changes that occur in a state impaired glucose tolerance are accompanied by the increased production of Th cell cytokines. The short-term treatment using low-dose aspirin combined with metformin may provide therapeutic benefits in preventing complications associated with dysregulated Th cell responses.