title: Thalidomide attenuates excessive inflammation without interrupting lipopolysaccharide-driven inflammatory cytokine production in chronic granulomatous disease.
abstract: 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.
authors.affiliation: Department of Human Genetics, National Center for Child Health and Development, Tokyo, Japan. kawai-t@ncchd.go.jp
authors.forename: Toshinao
authors.initials: T
authors.lastname: Kawai
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Watanabe
authors.forename: Midori
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Arai
authors.forename: Shinji
authors.initials: S
authors.lastname: Oana
authors.forename: Shizuko
authors.initials: S
authors.lastname: Harayama
authors.forename: Kozo
authors.initials: K
authors.lastname: Yasui
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Oh-Ishi
authors.forename: Masafumi
authors.initials: M
authors.lastname: Onodera
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D020170:Caspase 1 / Q000276:immunology; D002478:Cells, Cultured; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood / Q000276:immunology; D006105:Granulomatous Disease, Chronic / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D008070:Lipopolysaccharides; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D009163:Mycobacterium bovis; D016328:NF-kappa B / Q000276:immunology; D055732:Pulmonary Aspergillosis / Q000188:drug therapy / Q000276:immunology; D013792:Thalidomide / Q000627:therapeutic use*; D014376:Tuberculosis / Q000188:drug therapy / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide; D000255:Adenosine Triphosphate; D020170:Caspase 1