title: Effects of interferon-alpha on gene expression of chemokines and members of the tumour necrosis factor superfamily in HIV-infected patients.
abstract: We examined the effect of interferon (IFN)-alpha on the expression of 375 genes relevant to inflammatory and immunological reactions in peripheral blood mononuclear cells (PBMC) from HIV-infected patients by cDNA expression array and real-time quantitative RT-PCR. Our main findings were: (i) IFN-alpha induced up-regulation of several genes in the tumour necrosis factor (TNF) superfamily including the ligands APRIL, FasL, TNF-alpha and TRAIL, with particularly enhancing effects on the latter in HIV-infected patients. (ii) While IFN-alpha markedly up-regulated the expression of anti-angionetic ELR- CXC-chemokines (e.g. MIG and IP-10), it suppressed the expression of angiogenic ELR+ CXC-chemokines (e.g. GRO-alpha, IL-8 and ENA-78), with similar patterns in both patients and controls. (iii) IFN-alpha induced a marked increase in gene expression of the HIV co-receptor CCR5 in both patients and controls. We suggest that these effects may contribute to both the therapeutic and toxic effects of IFN-alpha. Moreover, our findings underscore that the biological effects of IFN-alpha in HIV infection are complex and that the clinical net effects of IFN-alpha treatment may be difficult to predict. However, the potent enhancing effect of IFN-alpha on several pro-apoptotic genes in the TNF superfamily and the enhancing effect on CCR5 expression suggest a possible pathogenic role of IFN-alpha in the progression of HIV-related immunodeficiency and suggests caution in the therapeutic use of IFN-alpha in HIV-infected -individuals.
authors.affiliation: Section of Clinical Immunology and Infectious Diseases, Research Institute for Internal Medicine, Rikshospitalet, Oslo, Norway.
authors.forename: E
authors.initials: E
authors.lastname: Stylianou
authors.forename: A
authors.initials: A
authors.lastname: Yndestad
authors.forename: L I
authors.initials: LI
authors.lastname: Sikkeland
authors.forename: V
authors.initials: V
authors.lastname: Bjerkeli
authors.forename: J K
authors.initials: JK
authors.lastname: Damås
authors.forename: T
authors.initials: T
authors.lastname: Haug
authors.forename: H G
authors.initials: HG
authors.lastname: Eiken
authors.forename: P
authors.initials: P
authors.lastname: Aukrust
authors.forename: S S
authors.initials: SS
authors.lastname: Frøland
mesh_terms: D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000235:genetics; D053222:Fas Ligand Protein; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D009479:Neuropeptides / Q000096:biosynthesis / Q000235:genetics; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000096:biosynthesis; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C490341:ANP32B protein, human; D051017:Apoptosis Regulatory Proteins; D018925:Chemokines; D019743:Chemokines, CXC; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D016898:Interferon-alpha; D008562:Membrane Glycoproteins; D009479:Neuropeptides; D009687:Nuclear Proteins; D012333:RNA, Messenger; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha