Interleukin-6 inhibition attenuates hypertension and associated renal damage in Dahl salt-sensitive rats.
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.
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin; and.
Shireen
S
Hashmat
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
Nathan
N
Rudemiller
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
Hayley
H
Lund
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
Justine M
JM
Abais-Battad
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin; and.
Scott
S
Van Why
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin dmattson@mcw.edu.
David L
DL
Mattson
D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D005434:Flow Cytometry; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015850:Interleukin-6 / Q000276:immunology* / Q000378:metabolism; D007674:Kidney Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007679:Kidney Medulla / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D020303:Rats, Inbred Dahl; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism
D057134:Antibodies, Neutralizing; D015850:Interleukin-6
cytokines; hypertension; immune system; kidney; rats