Interleukin-6 inhibition attenuates hypertension and associated renal damage in Dahl salt-sensitive rats. Am J Physiol Renal Physiol 2016 Sep 01;311(3):F555-61
Date
06/10/2016Pubmed ID
27279492Pubmed Central ID
PMC5142167DOI
10.1152/ajprenal.00594.2015Scopus ID
2-s2.0-84986192937 (requires institutional sign-in at Scopus site) 78 CitationsAbstract
Immune cells in the kidney are implicated in the development of hypertension and renal damage in the Dahl salt-sensitive (SS) rat. Interestingly, interleukin 6 (IL-6) mRNA is 54-fold higher in T-lymphocytes isolated from the kidney compared with circulating T-lymphocytes. The present experiments assessed the role of IL-6 in the development of SS hypertension by treating rats (n = 13-14/group) with an IL-6 neutralizing antibody or normal IgG during an 11-day period of high-salt (4.0% NaCl chow) intake. The mean arterial pressure (MAP) and urine albumin excretion rates (Ualb) were not different between the groups fed low salt (0.4% NaCl). Following 11 days of drug treatment and high salt, however, the rats receiving anti-IL-6 demonstrated a 47% reduction of IL-6 in the renal medulla compared with control SS. Moreover, the increase in MAP following 11 days of high-NaCl intake was significantly attenuated in SS administered anti-IL-6 compared with the control group (138 ± 3 vs. 149 ± 3 mmHg) as was the salt-induced increase in Ualb and glomerular and tubular damage. To investigate potential mechanisms of action, a flow cytometric analysis of immune cells in the kidney (n = 8-9/group) demonstrated that the total number of monocytes and macrophages was significantly lower in the treatment vs. the control group. The total number of T- and B-lymphocytes in the kidneys was not different between groups. These studies indicate that IL-6 production may participate in the development of SS hypertension and end-organ damage by mediating increased infiltration or proliferation of macrophages into the kidney.
Author List
Hashmat S, Rudemiller N, Lund H, Abais-Battad JM, Van Why S, Mattson DLMESH terms used to index this publication - Major topics in bold
AnimalsAntibodies, Neutralizing
B-Lymphocytes
Blood Pressure
Flow Cytometry
Hypertension
Interleukin-6
Kidney Diseases
Kidney Medulla
Male
Rats
Rats, Inbred Dahl
T-Lymphocytes
