Thalidomide has anti-inflammatory properties in neonatal immune cells.
Neonates demonstrate functional immaturity and dysregulation of immune responses leading to systemic inflammation and enhanced apoptosis of immune cells. Thalidomide has already been proven to differentially regulate immune responses and support anti-apoptosis in immunodeficiency syndromes. Thus, it was the aim of this study to evaluate the effects of thalidomide on the cytokine response and apoptosis of neonatal immune cells. After whole blood culture and stimulation of cord and adult blood samples, the intracytoplasmic expression and the secreted amounts of IL-2, TNF-α, IFN-γ, IL-6, IL-10 and IL-8 were assessed by flow cytometry and Cytokine Bead Array. Apoptosis was detected using Annexin-V staining. Bcl-2 expression was analysed using the Cytokine Bead Array Apoptosis Kit. Exposure to thalidomide (100 µg/ml) reduced the intracytoplasmic pro-inflammatory cytokine production of neonatal monocytes and the IFN-γ production of neonatal lymphocytes. In supernatants, the addition of thalidomide resulted in reduction of TNF-α, IL-6, IL-10 and, by trend, IFN-γ. While stimulated neonatal lymphocytes exhibited susceptibility to apoptosis, thalidomide tended to diminish apoptotic cells. Bcl-2 expression tended to be increased after addition of thalidomide. The potent anti-inflammatory effects of thalidomide and its anti-apoptotic properties in cord blood immune cells provide the basis for future strategies to optimise treatment of neonatal infections and immunodeficiency syndromes.
Department of Pediatrics, Albert-Ludwigs-University of Freiburg, Germany. alexander.puzik@uniklinik-freiburg.de
Alexander
A
Puzik
Annette
A
Thiel
Kirstin
K
Faust
Christoph
C
Härtel
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001773:Blood Cells / Q000187:drug effects* / Q000276:immunology; D002469:Cell Separation; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005312:Fetal Blood / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000188:drug therapy / Q000276:immunology*; D007231:Infant, Newborn; D007239:Infections / Q000188:drug therapy / Q000276:immunology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D013792:Thalidomide / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D019253:Proto-Oncogene Proteins c-bcl-2; D013792:Thalidomide