Thalidomide attenuates excessive inflammation without interrupting lipopolysaccharide-driven inflammatory cytokine production in chronic granulomatous disease

• Thalidomide suppressed TNFα-induced NF-κB activation in CGD monocytes.
• Thalidomide did not interrupt LPS-driven cytokine production in CGD monocytes.
• CGD monocytes released higher levels of IL-6 and TNF-α in response to LPS.
• Thalidomide reduced serum level of inflammatory cytokines in CGD colitis patient.
• Thalidomide did not impact immunity to pathogenic infections in CGD patient.

Chronic granulomatous disease (CGD) is a rare inherited disorder characterized by an inability to produce reactive oxygen species, resulting in recurrent life-threatening infections. Curiously, half of the patients with CGD suffer from aseptic bowel inflammation (CGD colitis) due to dysregulated inflammation induced by TNF-α and IL-1β. Thus, developing therapies that regulate excessive inflammatory responses without interrupting antimicrobial immunity would benefit CGD colitis patients. Here, we show that thalidomide suppressed TNF-α-induced NF-κB activation and ATP-induced IL-1β secretion, but did not interrupt the production of IL-1β, IL-6, IL-8, and TNF-α in response to lipopolysaccharide in CGD monocytes. We report on a CGD colitis patient that showed decreased bowel inflammation characterized by reduced serum levels of inflammatory cytokines without evidence of progression of fungal and bacterial infections present at initiation of thalidomide therapy. Our results suggest that thalidomide could be an efficacious therapeutic option for patients with CGD colitis suffering from serious infections.