IFN-alpha cannot substitute lack of IFN-gamma responsiveness in cells of an IFN-gamma R1 deficient patient

Author(s):
Wetering, D. van de; Wengen, A. van; Savage, N.D.L.; Vosse, E. van de; Dissel, J.T. van
Published
2011
Publication type
Article / Letter to editor

Abstract

Patients with complete IFN-gamma R deficiency are unable to respond to IFN-gamma and have impaired Th1-immunity and recurrent, severe infections with weakly virulent Mycobacteria. Since IFN-alpha and IFN-gamma share signalling pathways, treatment with IFN-alpha has been proposed in complete IFN-gamma R deficiency. We stimulated cells from healthy controls and from a patient lacking IFN-gamma R1 with IFN-alpha and IFN-gamma, to establish whether IFN-alpha would substitute for IFN-gamma effects. IFN-alpha induced STAT1 phosphorylation in monocytes of the IFN-gamma R1(-/-) patient, but did not prime for LPS-induced IL-12p70, IL-12p40, IL-23 or TNF production. In control cells, IFN-alpha inhibited the priming effect of IFN-gamma on LPS-induced pro-inflammatory cytokine release. Finally, IFN-gamma but not IFN-alpha induced killing of M. smegmatis in cultured macrophages. In conclusion, no evidence was found to support the use of IFN-alpha in IFN-gamma R-deficient patients as intervention against mycobacterial infection; on the contrary, treatment of individuals with IFN-alpha may even adversely affect host defence against Mycobacteria. (C) 2010 Elsevier Inc. All rights reserved.

IFN-alpha IFN-gamma IFN-gamma R1 deficiency Mycobacteria Mendelian susceptibility to mycobacterial disease Treatment avium complex infection interferon-gamma pulmonary tuberculosis interleukin-12 immunity expression mycobacteria macrophages inhibition monocytes
Date issued
2011-03-31
Language
English
Is part of
Clinical Immunology (2011), Vol. 138, no. 3, p. 282-290
hdl
1887/117778