Tumor necrosis factor and interleukin-1 may regulate renin secretion.
Cytokines such as tumor necrosis factor (TNF) and interleukin-1 (IL-1) are not only immunoregulatory polypeptides, but may have endocrine functions. We have studied the direct effects of recombinant and purified TNF and IL-1 on renin secretion using both static incubations and perifusions of rat renal cortical slices. Ultrapure human IL-1 (hIL-1) at concentrations as low as 5 U/ml (3 X 10(-12) M) significantly stimulated renin secretion (control, 98 +/- 4%; hIL-1, 153 +/- 13%; P less than 0.01). TNF similarly induced renin release [control, 97 +/- 6%; TNF (10 U/ml), 151 +/- 13%; P less than 0.005]. TNF and recombinant human IL-1 beta (rhIL-i beta) also blocked the inhibitory actions of angiotensin-II (AII) on renin release [control, 100 +/- 3%; AII (2 X 10(-7) M), 80 +/- 5%; AII plus TNF (20 U/ml), 102 +/- 7%; AII plus rhIL beta (10 U/ml), 106 +/- 6%; both P less than 0.02 vs. AII]. A cyclooxygenase (CO) blocker, meclofenamate (M), which does not significantly alter basal renin release, attenuated the TNF- and rhIL-1 beta-induced renin secretion [TNF (20 U/ml), 132 +/- 11%; TNF plus M (5 X 10(-5) M), 100 +/- 3% (P less than 0.01); rhIL-1 beta (10 U/ml), 135 +/- 9%; rhIL-1 beta plus M, 105 +/- 10% (P less than 0.05)]. The stimulatory effects of TNF and IL-1 on renin were reversible. These results suggest that IL-1 and TNF are renin secretagogues and can also block the inhibitory actions of AII on renin. Since the effect of TNF and IL-1 on renin can be blocked by a (CO) inhibitor, the studies indicate a role of prostaglandins in their action. Therefore, locally produced TNF and IL-1 may play an important paracrine role in regulation of the renin-angiotensin system.
Antonipillai
I
I
University of Southern California Medical Center, Section of Endocrinology, Los Angeles 90033.
Wang
Y
Y
Horton
R
R
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1 / Q000494:pharmacology*; D007606:Juxtaglomerular Apparatus / Q000166:cytology / Q000187:drug effects; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D008469:Meclofenamic Acid; D012083:Renin