CYTOKINE STORM and the INFLUENZA PANDEMIC: Treatment Options?ACE inhibitors and Angiotensin II Receptor Blockers: Genectoy and co-workers implicated the Renin Angiotensin system (RAS) in the mediation of the cytokine storm,[1] and these researchers suggested a potential benefit for Angiotensin Converting Enzyme (ACE) inhibitors and Angiotensin II Receptor Blockers (ARBs). Researchers at Johns Hopkins found ACE to be associated with inflammatory lung pathologies. [2] Shigehara et al. of Sapporo medical University in Japan published research confirming that serum angiotensin-converting enzyme (ACE) was a useful marker for disease activity in cytokine-mediated inflammatory lung diseases. [3] Marshall and co-workers similarly found that angiotensin II was associated with cytokine-mediated lung injury [4] and these researchers suggested a role for ACE inhibitors. Wang and co-workers published data that cytokine-mediated pulmonary damage (apoptosis of lung epithelial cells) in response to the pro-inflammatory cytokine TNF-alpha (implicated in the cytokine storm) requires the presence of angiotensin II, suggesting that ARBs might have clinical utility in this setting.[5] Das published a review of ACE inhibitor and angiotensin-II receptor blocker use in a number of cytokine-mediated inflammatory pathologies and found that angiotensin II was a pro-inflammatory molecule and suggested that ACE inhibitors and Angiotensin receptor blockers could have theoretical benefit in downregulation of the cytokine storm.[6] Vitamin D: Vitamin D reduces the risk of developing influenza [21,22], suppresses inflammatory cytokines [11, 12-14] and may suppress the cytokine storm associated with fatal cases of influenza [11,15]. Numerous studies have shown an increased risk for influenza when patients vitamin D levels decline. [16-20], and one recent study [23] found that risk was 36% higher for healthy people with vitamin D levels below 30 ng/ml. Additionally, a blinded, placebo controlled study conducted in 2005 found a direct correlation with with vitamin D supplementation and flu prevention [24]. Dosage: Vitamin D3 is the generally preferred form, and dosage may be in excess of 6,000 IU per day. Holick (University of Boston) found that Vitamin D toxicity does not typically develop unless vitamin D intake exceeds 10,000 units per day or blood levels exceed 80 ng/mL (200 nmol/L).[7,8] And Hathcock and co-workers stated that the tolerable upper intake level of vitamin D intake should be revised from 2,000 IU/day to 10,000 IU/day. [7] Holick suggests that optimum serum level of 25-hydroxyvitamin D is in the range of 30-50 ng/mL (75-125 nmol/L). [9] A study of elderly men and women by Dawson-Hughes et al suggested that levels of 25-hydroxyvitamin D above 45 ng/mL may be crucial for optimal health of all aging adults. [10] REFERENCES (1) Genctoy, G; B Altun et al. (February 2005). "TNF alpha-308 genotype and renin-angiotensin system in hemodialysis patients: an effect on inflammatory cytokine levels?". Artif Organs 29 (2): 174–178. (2) Moldobaeva, A; EM Wagner (December 2003). "Angiotensin-converting enzyme activity in ovine bronchial vasculature". J Appl Physiol (Department of Medicine, Johns Hopkins University) 95 (6): 2278–2284. (3) Shigehara, K; N Shijubo et al. (April 2003). "Increased circulating interleukin-12 (IL-12) p40 in pulmonary sarcoidosis". Clin Exp Immunol (Sapporo Medical University School of Medicine) 132 (1): 152–157. (4) Marshall, RP; P Gohlke et al. (January 2004). "Angiotensin II and the fibroproliferative response to acute lung injury". Am J Physiol Lung Cell Mol Physiol (Royal Free and University College London Medical School) 286 (1): 156–164. PMID 12754187. (5) Wang, R; G Alam et al. (November 2000). "Apoptosis of lung epithelial cells in response to TNF-alpha requires angiotensin II generation de novo". J Cell Physiol (The Cardiovascular Institute, Michael Reese Hospital and Medical Center) 185 (2): 253–259. PMID 11025447. (6) Das UN (May 2005). "Angiotensin-II behaves as an endogenous pro-inflammatory molecule". The Journal of the Association of Physicians of India 53: 472–6. (7) Hathcock JN, Shao A, Vieth R, Heaney R. Risk assessment for vitamin D. Am J Clin Nutr. 2007 Jan;85(1):6-18. (8) Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc. 2006 Mar;81(3):353-73. (9) Holick MF. The role of vitamin D for bone health and fracture prevention. Curr Osteoporos Rep. 2006 Sep;4(3):96-102. (10) Dawson-Hughes B, Harris SS, Dallal GE. Plasma calcidiol, season, and serum parathyroid hormone concentrations in healthy elderly men and women. Am J Clin Nutr. 1997 Jan;65(1):67-71 (11) Virol J. 2008;529. (12) Blood 2005 Dec 15;106(13):4351-8 (13) Br J Nutr. 2005 Oct;94(4):483-92 (14) Mol Aspects med. 2008 Dec;29(6):369-75 (15) Mikrobiyol Bul. 2008 Apr;42(2):356-80 (16) Eur J Clin Nutr. 2004 Apr;58(4):563-7. (17) Am J Clin Nutr. 2007 Sept;86(3):714-7. (18) J Infect Dis. 2008 Mar 1;197(5)676-80. (19) Eur J Clin Nutr. 2009 Apr;63(4):473-7 (20) Pediatr Pulmonol. 2009 Sept 10;44(10):981-8. (21) Science News. 2006 Nov 11:312-3. (22) J Nutr. 2005 Feb;135:(2):317-22. (23) Arch Intern Med. 2009 Feb 23;169(4):384-90. (24) Epidemiol Infect. 2007 Oct;135(7):1095-6.  home | H1N1 Mexican Swine flu | Germany | United States, United Kingdom, New Zealand, France, Finland, Norway, and Switzerland | World Health Organization | Bird Flu from a Vaccination | Bird Flu: Is there an effective Vaccination? | Bird Flu: Evidence of Human to Human transmission? | |