Effects of Chronic Intraperitoneal Curcumin Administration on Tissue‐Specific Inflammation in a Murine Model of Systemic Lupus Erythematosus

Chronic inflammation has been implicated in the pathogenesis of hypertension and our lab uses a model of systemic lupus erythematosus (SLE) to study this relationship. SLE is an autoimmune disorder that primarily affects reproductive age women, and there is a high prevalence of renal injury and hypertension in patients with the disease. In addition, SLE is associated with diminished autonomic (vagal) tone and dysregulated neuroendocrine/neuroimmune mechanisms—one example being the hypothalamic‐pituitary‐adrenal (HPA) axis, which can be activated by the afferent vagus nerve and whose impairment results in inadequate basal plasma cortisol that can promote chronic inflammation in SLE. Curcumin, the active component of the spice turmeric that is thought to have anti‐inflammatory properties, activates vagal afferents via TRPA1 channels. Therefore, we hypothesize that chronic curcumin administration increases HPA axis function and heightens cortisol release in SLE, and that this protects against tissue‐specific inflammation. Previous studies in our laboratory demonstrated that chronic intraperitoneal administration paradoxically increased inflammatory markers in the renal cortex and medulla, as well as the spleen. Because these results could potentially be due to repeated peritoneal injection, we repeated the study and focused on inflammation in other organs that are major sites of the reticuloendothelial system: the liver and lungs. Thirty‐week old female SLE ( NZBWF1 ) and control ( NZW ) mice (n = 4–5 mice/group) were administered curcumin (50 mg/kg in sesame oil; i.p. injections) or vehicle daily for 28 days. Mice were euthanized at the end of the study and livers and lungs were harvested. Liver tumor necrosis factor (TNF)‐a (pro‐inflammatory cytokine measured by Western blot and normalized to total protein) was not significantly elevated in SLE mice in relation to control mice (3.0e6 ± 1.7e6 vs 1.1e6 ± 1.5e5; p = 0.560), but was increased in curcumin‐treated SLE mice (6.1e6 ± 1.3e6; p = 0.028). Lung TNF‐a was elevated in SLE mice compared to controls (1.3e7 ± 1.3e6 vs 7.7e6 ± 2.0e5; p = 0.004), while curcumin treatment did not alter its expression in SLE mice (1.3e7 ±1.3e6; p = 0.941). Lung IL‐10 (anti‐inflammatory cytokine) was not significantly elevated in SLE mice in relation to control mice (2.1e7 ± 3.0e6 vs 2.2e7 ± 5.5e6; p = 0.825), but was increased in curcumin‐treated SLE mice (3.6e7 ± 5.0e6; p = 0.010). The results indicate that chronic intraperitoneal curcumin administration produced differential responses: inflammatory effects in the liver (just as in the kidney and spleen) and anti‐inflammatory effects in the lung. Taken together, the damage caused by curcumin on abdominal organs counter the prevailing theory of curcumin's protective actions. Our findings suggest that daily peritoneal curcumin administration may be injurious due to the relative lack of a protective fibrous peritoneum overlying the kidneys, spleen and liver. Support or Funding Information Funded by AHA grants 14SDG18320033 (KWM), 16PRE29910012 (GSP), and UNTHSC Intramural Funding This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .