Table 1 Complex relation between TNFα and type I IFN in human studies
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 | [9] | |
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] |