Tumor Necrosis Factor and Interleukin-1 May Regulate Renin Secretion*

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Abstract
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 renln 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 × 10-12 M) significantly stimulated renin secretion (control, 98 ± 4%; hIL-1, 153 ± 13%; P < 0.01). TNF similarly induced renin release [control, 97 ± 6%; TNF (10 U/ml), 151 ± 13%; P < 0.005]. TNF and recombinant human 1L-1β (rhlL-iβ) also blocked the inhibitory actions of angiotensin-II (All) on renin release [control, 100 ± 3%; All (2 × 10-7 M), 80 ± 5%; All plus TNF (20 U/ml), 102 ± 7%; All plus rhILβ (10 U/ml), 106 ± 6%; both P < 0.02 vs. All]. A cyclooxygenase (CO) blocker, meclofenamate (M), which does not significantly alter basal renin release, attenuated the TNF- and rhlL-1β-induced renin secretion [TNF (20 U/ml), 132 ± 11%; TNF plus M (5 × 10-5 M), 100 ± 3% (P < 0.01); rhIL-1β (10 U/ml), 135 ± 9%; rhIL-1β plus M, 105 ± 10% (P < 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 All 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-anglotensin system. (Endocrinology126: 273–278, 1990)