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Table 1 Complex relation between TNFα and type I IFN in human studies

From: Type I IFN and TNFα cross-regulation in immune-mediated inflammatory disease: basic concepts and clinical relevance

Cross- regulation Cell type Activation state Experimental model Results Reference
TNF↓ IFN ↑ PBMCs JIA Anti-TNFα-treated vs. untreated patients Patients treated with anti-TNFα showed higher IFNα-regulated genes [8]
  PBMCs Healthy In vitro culture with etanercept Dose-dependent increase in transcription of
IFNα inducible genes
  Blood RA Infliximab-treated RA patients Upregulation of type I IFN response genes only in patients with a poor clinical response [52]
  Serum SpA Etanercept-treated SpA patients (all good clinical response) Small increase in IFNα activity after 12 weeks of treatment [53]
  Plasma SS Etanercept-treated SS patients (poor clinical response) Increase plasma in IFNα activity after 12 weeks of treatment [9]
  Plasma Inflammatory myopathy Infliximab-treated patients (no clinical response) Increase in serum type I IFN activity [55]
TNF ↓ IFN ↓ Serum SpA Infliximab-treated SpA patients (all good clinical response) Slightly decrease in IFNα activity after 2 weeks that returns to baseline after 12 weeks [53]
TNF ↑ IFN ↓ pDC Influenza virus Incubation of virus-activated pDC with TNFα TNFα inhibited IFNα, probably due to pDC maturation [8]
TNF ↑ IFN ↑ Fibroblasts Healthy In vitro stimulation with TNFα TNFα induced IFNβ mRNA levels [10]
  Macrophages Healthy In vitro stimulation with TNFα TNFα induced type I IFN response program through IFN regulatory factor-1, leading to an IFNβ-mediated autocrine loop [11]
  Serum Juvenile DM TNF-308 promotor polymorphism Only in untreated patients: increased levels IFNα in carriers of minor allele, which is associated with increased TNFα production [43]
  PBMCs RRMS Concanavalin A-stimulated PBMCs obtained from IFNβ-treated MS patients More production of TNFα in concanavalin A-stimulated PBMCs after IFNβ treatment [57]
  Monocytes Healthy Pre-incubation (30 min) with IFNβ, subsequent stimulation with LPS IFNβ pretreatment enhanced LPS-induced TNFα production by monocytes [17]
INF ↑ TFN ↓ Macrophages Healthy In vitro pretreatment with IFNα (100 U/ml) and subsequent immune complexes, Fc receptor or TLR stimulation IFNα suppressed FcγR-induced, TLR2-induced and TLR4-induced TNFα production through induction of Axl, a repressor of TNFα promoter [15]
  PBMCs RRMS Anti-CD3-stimulated PBMCs obtained from IFNβ-treated MS patients IFNβ therapy decreased the production of TNFα by anti-CD3-stimulated PBMCs [57]
  Synovial tissue RA Type I IFN treatment of RA patients Decreased levels of TNFα in synovial tissue in some patients [58]
  PBMCs Healthy PHA and IFNβ-treated PBMCs IFNβ decreased PHA-induced TNFα production by PBMC [12]
  Co-cultures of T lymphocytes and monocytes Healthy Co-cultures of T lymphocytes and monocytes stimulated by PHA in the presence of IFNβ IFNβ inhibits the ability of stimulated T lymphocytes to induce cell contact-mediated TNFα production in monocytes [13]
  THP-1 Cell line Pre-incubation (24 hours) with IFNβ1b, subsequent stimulation with LPS in the presence or absence of dexamethasone LPS-induced TNFα production by THP-1 cells was suppressed by dexamethasone. This suppressive effect was augmented by pre-incubation with IFNβ [14]
  Monocytes Healthy Pre-incubation (30 min) with IFNβ, subsequent stimulation with plasma membranes of PHA + PMA-stimulated HUT-78 cells Pretreatment with IFNβ decreased TNFα production by contact-activated monocytes [17]
  PBMCs Healthy IFNβ administration and ex vivo mitogen stimulation of PBMCs IFNβ induced a transient decrease of inflamatory cytokines including TNFα [56]
INF ↓ TFN ↓ Blood and skin lesions SLE Treatment with an anti-IFNα antibody in SLE patients Downmodulation of TNFα mRNA levels [59]
  1. DM, dermatomyositis; HUT-78, human T-cell line; JIA, juvenile idiopathic arthritis; LPS, lipopolysaccharide; MS, multiple sclerosis; PBMC, peripheral blood mononuclear cell; pDC, plasmacytoid dendritic cells; PHA, phytohemagglutinin; PMA, phorbol myristate acetate; RA, rheumatoid arthritis; RRMS, relapsing-remitting multiple sclerosis; SLE, systemic lupus erythematosus; SpA, spondyloarthritis; SS, Sjögren's syndrome; THP-1, human monocytic cell line.