Interleukin-6 inhibition attenuates hypertension and associated renal damage in Dahl salt-sensitive rats

Shireen Hashmat, Nathan Rudemiller, Hayley Lund, Justine M. Abais-Battad, Scott Van Why, David L. Mattson

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)F555-F561
JournalAmerican Journal of Physiology - Renal Physiology
Volume311
Issue number3
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

Fingerprint

Inbred Dahl Rats
Renal Hypertension
Interleukin-6
Salts
Kidney
Arterial Pressure
Macrophages
Hypertension
T-Lymphocytes
Control Groups
Neutralizing Antibodies
Action Potentials
Monocytes
Albumins
B-Lymphocytes
Immunoglobulin G
Urine
Messenger RNA

Keywords

  • Cytokines
  • Hypertension
  • Immune system
  • Kidney
  • Rats

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Interleukin-6 inhibition attenuates hypertension and associated renal damage in Dahl salt-sensitive rats. / Hashmat, Shireen; Rudemiller, Nathan; Lund, Hayley; Abais-Battad, Justine M.; Van Why, Scott; Mattson, David L.

In: American Journal of Physiology - Renal Physiology, Vol. 311, No. 3, 01.01.2016, p. F555-F561.

Research output: Contribution to journalArticle

Hashmat, Shireen ; Rudemiller, Nathan ; Lund, Hayley ; Abais-Battad, Justine M. ; Van Why, Scott ; Mattson, David L. / Interleukin-6 inhibition attenuates hypertension and associated renal damage in Dahl salt-sensitive rats. In: American Journal of Physiology - Renal Physiology. 2016 ; Vol. 311, No. 3. pp. F555-F561.
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