CDK4/6 inhibitor palbociclib reduces inflammation in lupus-prone mice

Lupus is an autoimmune inflammatory disease that affects multiple organs. Cyclin-dependent kinases (CDKs) have been associated with inflammation. The objective of this study was to explore the effects of palbociclib (a CDK4/6 inhibitor) on inflammation in a lupus-prone MRL-lpr mouse model. Twenty mice (10 females and 10 males) were randomized into control group (n=10, treated with vehicle) and treatment group (n=10, treated with 3 cycles of palbociclib at a dose of 120 mg/kg/day for 2 weeks on and 10 weeks off, through oral gavage). Animals were euthanized after the third cycle of treatment. We found that facial skin lesions developed later and smaller in the female mice treated with palbociclib than the female mice in the control group. The lymph node number was less and the lymph node weight was lighter in the female treatment group compared to the female control group. The inflammatory lesions in the kidneys of male mice treated with palbociclib were significantly reduced compared to the male mice in the control group. Our findings suggest that palbociclib treatment reduces inflammation in lupus-prone mice in a gender-specific manner, targeting the facial skin and lymph nodes in the female mice and the kidneys in the male mice.