IFN-α cannot substitute lack of IFN-γ responsiveness in cells of an IFN-γR1 deficient patient

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• 作者：Diederik van de Wetering^a ; Annelies van Wengen^a ; Nigel D.L. Savage^a ; Esther van de Vosse ; ^a ; ^{E.van_de_Vosse@lumc.nl} ; Jaap T. van Dissel^a
• 关键词：IFN-α ; IFN-&#x3b3 ; IFN-&#x3b3 ; R1 deficiency ; Mycobacteria ; Mendelian susceptibility to mycobacterial disease ; Treatment
• 刊名：Clinical Immunology
• 出版年：2011
• 出版时间：March 2011
• 年：2011
• 卷：138
• 期：3
• 页码：282-290
• 全文大小：813 K

文摘

Patients with complete IFN-γR deficiency are unable to respond to IFN-γ and have impaired Th1-immunity and recurrent, severe infections with weakly virulent Mycobacteria. Since IFN-α and IFN-γ share signalling pathways, treatment with IFN-α has been proposed in complete IFN-γR deficiency. We stimulated cells from healthy controls and from a patient lacking IFN-γR1 with IFN-α and IFN-γ, to establish whether IFN-α would substitute for IFN-γ effects. IFN-α induced STAT1 phosphorylation in monocytes of the IFN-γR1^­/­ patient, but did not prime for LPS-induced IL-12p70, IL-12p40, IL-23 or TNF production. In control cells, IFN-α inhibited the priming effect of IFN-γ on LPS-induced pro-inflammatory cytokine release. Finally, IFN-γ but not IFN-α induced killing of M. smegmatis in cultured macrophages. In conclusion, no evidence was found to support the use of IFN-α in IFN-γR-deficient patients as intervention against mycobacterial infection; on the contrary, treatment of individuals with IFN-α may even adversely affect host defence against Mycobacteria.