Decreased interferon-α and interferon-β production in obesity and expression of suppressor of cytokine signaling

Abstract Objective We analyzed the interferon-α (IFN-α), IFN-β, and proinflammatory responses induced by Toll-like receptor (TLR) ligands in peripheral blood mononuclear cells (PBMCs) from obese subjects and their association with suppressor of cytokine signaling-1 (SOCS1) and SOCS3 expression. Methods The IFN responses were measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay in PBMCs stimulated with TLR-3 and TLR-7 ligands from 30 non-obese (body mass index ≤25 kg/m2 ) and 30 obese (body mass index ≥30 kg/m2 ) volunteers. The mRNA expression of nuclear factor-κB, SOCS1, and SOCS3 also was evaluated by qRT-PCR. Proinflammatory cytokine responses were measured by enzyme-linked immunosorbent assay. Results Obese subjects showed a decreased ability to produce IFN-α and IFN-β in response to TLR ligands; this response was associated with increased basal levels of SOCS3 but not SOCS1. However, after stimulation, the expression of SOCS3 and SOCS1 mRNA was significantly lower in PBMCs from obese compared with non-obese subjects. The PBMCs from obese subjects also showed higher basal levels of interleukin-6 and a decreased response of proinflammatory cytokines interleukin-6 and interleukin-1β after stimulation with the TLR-3 ligand compared with PBMCs from non-obese participants. Conclusion These data suggest that obesity is related to impaired IFN-α and IFN-β responses and increased SOCS3 basal mRNA expression and that a signaling pathway by TLR-3 may be involved. These results could explain, at least in part, the inadequate response of obese people against viral infections, such as influenza.