That's interesting. The vaccine isn't what they are crediting with reversal of diabetes or multiple sclerosis. It's the TNF. Which...drum roll please...inhibits aldosterone production!http://endo.endojournals.org/content/125/6/3084.short
Tumor Necrosis Factor and Interleukin-1 Are Potent Inhibitors of Angiotensin-II-Induced Aldosterone Synthesis*
R. HORTON and
- Author Affiliations
Section of Endocrinology, University of Southern California-Los Angeles County Medical Center Los Angeles, California 90033
Address requests for reprints to: Rama Natarajan, Ph.D., Section of Endocrinology, University of Southern California Medical Center, Room 18632, 2025 Zonal Avenue, Los Angeles, California 90033.
Cytokines such as tumor necrosis factor (TNF) and interleukin-1 (IL-1), mediate many inflammatory and cellular responses. However, the effects of TNF and IL-1 on basal and angiotensin-II (All)-stimulated aldosterone synthesis are not known. We studied the effect of recombinant and purified TNF and IL-1 on basal as well as All-, ACTH-, and K+-induced aldosterone synthesis in isolated rat adrenal glomerulosa cells. Since we have previously shown that All action is mediated by activation of the 12-lipoxygenase (12LO) pathway of arachidonic acid, we also evaluated the effects of these cytokines on the 12LO product 12-hydroxyeicosatetraenoic acid (12HETE) using a validated RIA technique. TNF at 2.5 and 5.0 ng/ml produced a dose-dependent inhibition of All-induced aldosterone synthesis [All, 39.0 ± 3.3 ng/106 cells-h; All plus TNF (5.0 ng/ml), 14.3 ± 1.6; P < 0.001 vs. All; All plus TNF (2.5 ng/ml), 24.7 ± 3.2; P < 0.01 vs. All]. Similarly, TNF at 5.0 ng/ml also attenuated the stimulatory effect of ACTH (10−9 M). However, K+- induced aldosterone synthesis was not altered. TNF also did not alter basal aldosterone levels. All, as previously shown, stimulates 12HETE synthesis (basal, 608 ± 114 pg/105 cells-h; versus All, 1268 ± 197; P < 0.02). TNF at concentrations of 1.0–5.0 ng/ml produced a dose-dependent inhibition of All stimulatory action on 12HETE synthesis [All plus TNF (1.0 ng/ml), 650 ± 26 pg, P < 0.03 vs. All; All plus TNF (5.0 ng/ml), 390 ± 46; P < 0.01 vs. All plus TNF (1.0 ng/ml)]. In addition, 12HETE at 10−8 M completely restored the effects of All during blockage by TNF. Purified human IL-1 (75% β, 25% α) as well as recombinant human IL-1β at concentrations as low as 50 pg/ml inhibited All-induced aldosterone synthesis. IL-1β did not alter ACTHor K+-induced aldosterone synthesis and, in fact, had a tendency to potentiate ACTH effects. These results suggest that the cytokines TNF and IL-1 are potent inhibitors, particularly of All action in the adrenal glomerulosa cell. Therefore, local or systemically produced TNF or IL-1 may be important negative modulators of aldosterone synthesis.