IL‐10 Supplementation Decreases BP in Male, But Not Female, Spontaneously Hypertensive Rats
Authors: Gillis Ellen E , Hutchinson Justin , Musall Jacqueline B. , Sullivan Jennifer C. 
Published: November 2023

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 yet been studied. For the current study, we hypothesized that chronic infusion of IL‐10 in hypertensive rats would lower BP concomitant with an increase in NO synthase (NOS) activity. First, endogenous basal levels of renal IL‐10+ cells and the IL‐10 receptor were measured in a subset of male and female spontaneously hypertensive rats (SHR). In a second set of rats, baseline BP was recorded by tail cuff plethsmography, and rats were placed in metabolic cages for 24‐hr urine collection prior to initiating infusion of IL‐10. IL‐10 was infused by subcutaneous minipump (3.5 ug/kg/d) in half of the male and female SHR, with the remaining rats serving as sham controls (n=4–6 per treatment group per sex). After 2 weeks of treatment, final BP and metabolic cage timepoints were collected, and tissues were harvested. Female SHR had greater IL‐10+ renal cells than males (flow cytometry, 4.6±0.4 vs 1.9±0.4%, p=0.003, n=8) and greater expression of the IL‐10 receptor (Western blot, 0.4±0.1 vs 0.13±0.1 densitometric units, p=0.03, n=4). BP did not change in female SHR treated with IL‐10 (2‐way ANOVA, p=0.3), but BP significantly decreased following IL‐10 infusion in male rats (p=0.04, Table); BP was higher in males than females in both groups (p<0.001). Urinary protein excretion (Bradford assay) did not differ between treatment and control groups in either sex (Table); but excretion was higher in males than in females (p=<0.001). Contrary to our hypothesis, NOS enzymatic activity (measured by the conversion of radio‐labeled arginine to radio‐labeled citrulline) significantly decreased with IL‐10 treatment in both the inner medulla (p=0.004) and the renal cortex (p=0.003) of both sexes (Table). In conclusion, despite the finding that male SHR have less IL‐10 and IL‐10 receptor expression in the kidney compared to females, BP was selectively decreased in males. We hypothesize that the higher endogenous levels of IL‐10 in the female SHR contribute to the observed sex difference in BP and prevent further decreases in BP with exogenous IL‐10 infusion. Furthermore, our data suggests that decreases in BP in male SHR with IL‐10 is not dependent on upregulating NOS activity in the kidney, although the effect of IL‐10 on NO bioavailability was not assessed. Future studies will further explore the role of endogenous IL‐10 on BP control in female SHR.

Baseline BP (mmHg)
Final BP (mmHg)
Baseline Proteinuria (mg/d)
Final Proteinuria (mg/d)
Inner Medulla NOS activity (pmol/mg)
Cortex NOS activity (pmol/mg)

Male CON
211±1
221±5
10±1
15±2
780±123
17287±42772

Male IL‐10
213±5
200±4*
12±1
16±2
284±29*
7316±1917*

Female CON
160±8#
169±7#
2±0.4#
3±1#
1296±213#
20260±2207

Female IL‐10
163±2#
169±9#
1±0.3#
2±0#
650±65*#
8279±1215*

p<0.05 vs CON same sex,
p<0.05 vs male same treatment