Lupus is an autoimmune disease that causes long-term inflammation in organs like the kidney and the skin. The long-term inflammation also contributes to the chronic pain and fatigue that most lupus patients experience. The symptoms of lupus are currently treated with medication that reduce inflammation, like steroids, but long-term steroid therapy also causes other unwanted harm to the body. The goal of our proposal is to develop a new therapeutic option, ultrasound, to decrease inflammation with no side effects.

Ultrasound would not be used in the conventional way in our studies. The reason it is a viable option is because ultrasound at certain frequencies is capable of increasing nerve activity. The spleen and splenic nerve are in close proximity to the left kidney, and are easily located and visualized by applying the ultrasound to the left flank on an anesthetized mouse. Ultrasound of that region on the left flank of the mouse can lead to an increase splenic nerve activity. The activated splenic nerve suppresses inflammatory processes in the spleen and this leads to reduced inflammation throughout the body. Based on this, we hypothesize that if we stimulate the splenic nerve in mice with lupus via ultrasound, inflammation and end-organ damage would be reduced and so would morbid outcomes associated with lupus.

To determine if this new and exciting use of ultrasound is beneficial in lupus, we will start by using a mouse model of lupus that has been used in the research laboratory setting over 50 years. This model has been shown numerous times to mimic human lupus in that the mice have the same disease biomarkers and disease course. We will increase splenic nerve activity for both short- and long-term periods in female and male lupus mice electrically, with chemicals, and via ultrasound. These studies will examine the effect of this splenic nerve manipulation on immediate inflammatory responses in the blood, kidneys, and other organs harmed in lupus, and after long-term ultrasound therapy. We will also determine if this therapy would be beneficial for both female and male lupus since we know that lupus develops differently depending on the sex. Ultimately, this work will allow us to determine biological mechanisms of lupus disease and the pathobiology of end organ injury in lupus. Findings from our studies would set the groundwork and clearly explain how ultrasound is protective, so that this novel, portable, and harmless method can be tested in human patients with lupus.