MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) DECREASES NEUROINFLAMMATION IN THE SOLITARY TRACT NUCLEUS (NTS) OF SPONTANEOUSLY HYPERTENSIVE RATS (SHR).

• DOI: 10.1096/fasebj.27.1_supplement.1118.2
• Publication Date: 2021-06-21T14:59:00Z
• Authors: Andre H Freiria‐O...; Graziela T Blanch; Hongwei Li; Debora S A Colombari; Eduardo Colombari; Colin Sumners
• Keywords: 0301 basic medicine; 03 medical and health sciences

Increasing MIF levels in the NTS reduces blood pressure in SHR. Since inflammation has an important role in hypertension we investigated whether increasing MIF in the NTS of SHR alters inflammatory cytokine levels and microglial activation. Male SHR and normotensive (NT) rats (8 weeks old) were microinjected in the NTS with either AAV2‐CBA‐MIF or AAV2‐CBA‐eGFP to elicit chronic increases in MIF and GFP (control) expression. Thirty days later, we analyzed inflammatory cytokine mRNAs or microglial activation in the NTS. Baseline levels of pro‐inflammatory cytokine (PIC) mRNAs such as IL‐1β, IL‐6 and TNFα were significantly greater (0.5 to 3 fold) in the NTS of SHR vs. NT rats (p<0.05). The baseline level of IL‐10 mRNA (anti‐inflammatory cytokine) was significantly reduced by 3 fold in SHR vs. NT rats. MIF over expression in the NTS did not alter cytokine mRNA levels in NT rats, but in SHR normalized the levels of PIC and IL‐10 mRNAs in the NTS towards those observed in NT rats (p<0.05). Qualitative assessment of microglial activation via Iba‐1 immunohistochemistry indicated greater microglial activation in the NTS of SHR vs. NT rats, and this was reversed by MIF over expression. The results suggest that MIF over expression in the NTS of SHR can reduce neuroinflammation at this site, and this may contribute to the reduce blood pressure observed in these animals.Grant Support: FAPESP/PRONEX, CNPq, NIH (HL076803)