IL-10 treatment decreases blood pressure in male, but not female, spontaneously hypertensive rats.

Interleukin 10 (IL-10) is an anti-inflammatory cytokine that induces nitric oxide (NO) production. IL-10 supplementation has previously been shown to lower blood pressure (BP) in male hypertensive mice, but the effect of exogenous IL-10 in hypertensive females has not been studied. For the current study, we hypothesized that chronic infusion of IL-10 in hypertensive rats would lower BP concomitant with increased renal NO synthase (NOS) activity. Male and female spontaneously hypertensive rats (SHR, 12 weeks old) were randomized to receive IL-10 infusion by subcutaneous mini-pump (3.5 µg/kg/day) or serve as sham controls (n=4-6 per treatment per sex). BP was measured by tail cuff before and after two weeks of treatment. Renal T cells and IL-10 were measured by flow cytometry and NOS activity was determined by conversion of radio-labeled arginine to radio-labeled citrulline. Female SHR had greater IL-10+ renal cells than males and greater expression of the IL-10 receptor at baseline. BP did not change in female SHR treated with IL-10, but BP significantly decreased following IL-10 infusion in male rats. Contrary to our hypothesis, NOS enzymatic activity decreased with IL-10 treatment in the renal inner medulla and cortex of both sexes. Renal Tregs also decreased in both sexes after IL-10 treatment. In conclusion, despite male SHR having less IL-10 and IL-10 receptor expression in the kidney compared to females, exogenous IL-10 selectively decreased BP only in males. Furthermore, our data suggests that exogenous IL-10-induced decreases in BP in male SHR are not dependent on upregulating renal NOS activity.