Targeting nicotinic receptors to reduce inflammation associated with SLE

Chronic, long-term inflammation can damage organs throughout the body, including the brain, in people with lupus. Dr. Mathis has discovered that nicotine, a chemical found in tobacco products, can reduce inflammation; however, nicotine is too toxic overall to be used as a treatment in people with lupus. In this exciting translational project, Dr. Mathis is exploring other, nontoxic molecules that might work like nicotine to heal inflammation, but without causing serious side effects. In addition, she will examine whether this type of therapy can reduce inflammation in the brain and, in turn, eliminate negative behavior changes caused by lupus.

What this study means for people with lupus

Dr. Mathis hopes to identify a new treatment for chronic inflammation in lupus that is safe, highly effective, and free of toxic side effects. Importantly, her Novel Research Grant will show whether reducing inflammation in the brain with such treatments can reverse behavioral symptoms of lupus.

Chronic systemic inflammation is an underlying mechanism in the pathogenesis of systemic lupus erythematosus (SLE); therefore, therapies that target inflammation are warranted. Preliminary studies in our lab indicate that subcutaneous nicotine attenuates tissue-specific inflammation in a well-established murine model of SLE. Because of the toxic and addictive nature of nicotine, it could never be used as a therapy for lupus patients. We propose to treat SLE mice with a positive allosteric modulator and a selective agonist of the a7-subunit of the nicotinic acetylcholine receptor (a7-nAChR) to determine if it indeed reduces peripheral and central inflammation in both female and male SLE mice. In addition, we will test whether the behavioral phenotype of lupus mice is improved following this anti-inflammatory therapy. These studies are timely given the recent interest in the novel vagus nerve-to-spleen mechanism termed the cholinergic anti-inflammatory pathway. The a7-nAChR is a critical component of this protective endogenous pathway and should be targeted to quell inflammation in SLE.