IL-36-Induced Toxicity in Neonatal Mice Involves TNF-α Production by Liver Myeloid Cells
| Autor: | Beatris Mastelic-Gavillet, Jennifer Palomo, Claire-Anne Siegrist, Gaby Palmer, Estelle Woldt, Emiliana Rodriguez, Cem Gabay, Sabina Troccaz |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Myeloid Tetanus Toxoid/toxicity medicine.medical_treatment Immunology Tumor Necrosis Factor-alpha/biosynthesis Pharmacology Myeloid Cells/immunology Proinflammatory cytokine Cytokines/biosynthesis 03 medical and health sciences chemistry.chemical_compound Mice Liver/immunology medicine Tetanus Toxoid Interleukin-1/toxicity Immunology and Allergy Animals Myeloid Cells ddc:618 Alum business.industry Tumor Necrosis Factor-alpha Toxoid 3. Good health Mice Inbred C57BL Haematopoiesis 030104 developmental biology medicine.anatomical_structure chemistry Animals Newborn Liver Toxicity Cytokines Tumor necrosis factor alpha business Adjuvant Interleukin-1 |
| Zdroj: | Journal of immunology (Baltimore Md. : 1950) Journal of Immunology, Vol. 197, No 6 (2016) pp. 2239-49 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Human and mouse neonates exhibit limited vaccine responses characterized by predominant Th2 and limited Th1 responses. Because IL-36 exerts a synergic adjuvant effect with IL-12, enhancing Th1 polarization in adult (AD) mice, we administered IL-36β to neonatal (1-wk old) and AD control mice at the time of immunization with tetanus toxoid adsorbed to aluminum hydroxide (TT/Alum). Unexpectedly, the combination of IL-36β with TT/Alum, which was well tolerated in AD mice, proved toxic and even lethal in neonates. This neonatal toxicity was associated with high Il36r mRNA expression in neonatal liver, resulting in increased cytokine production. Liver Il36r mRNA expression decreased with the termination of fetal liver hematopoiesis, and this decrease correlated with a complete protection from TT/Alum/IL-36β–induced mortality. The combination of IL-36β and TT/Alum induced the rapid production of TNF-α and IFN-γ by liver myeloid and lymphoid cells, respectively. These responses were less marked when IL-36β was used alone, with no adverse effect. The toxicity of IL-36β + TT/Alum was abrogated by the administration of a neutralizing anti–TNF-α Ab, confirming causality. In conclusion, liver myeloid cells in neonatal mice are an important source of proinflammatory cytokines that may lead to TNF-α–mediated toxicity and even lethality. |
| Databáze: | OpenAIRE |
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