Interleukin-6 Antagonists for the Management of Hypertension
To the Editor:
I read with great interest the recent article published by Luther et al1 in the December 2006 issue of Hypertension, which focused on how angiotensin II induces interleukin (IL)-6 in humans. The authors suggest that angiotensin II performs this function through a mineralocorticoid receptor–dependent mechanism.
I would like to suggest the possible future role of IL-6 antagonists in the control and treatment of recalcitrant hypertension. Abnormal IL-6 levels have been noted in almost all types of inflammatory disorders. Abnormal IL-6 production has also been noted in acute coronary syndromes2 and a number of malignancies, such as multiple myeloma. It is widely believed that IL-6 may have a major role to play in the pathogenesis of almost all inflammatory disorders in the body.
Manfredini et al3 reported the development of an IL-6 peptide antagonist that was shown to reduce IL-6 activity in vitro. Another molecule that is currently being studied is tocilizumab. Tocilizumab is an antihuman IL-6 receptor antibody of the IgG1 subclass currently used primarily in the treatment of rheumatoid arthritis. It binds to both the soluble and the membrane-bound forms of IL-6 receptors, thus markedly reducing binding of IL-6 to its receptors and, thus, reducing its proinflammatory function.4 Molecules such as tocilizumab have shown considerable promise as IL-6 antagonists and may play a vital role in management of recalcitrant hypertension in the near future.
Luther JM, Gainer JV, Murphey LJ, Yu C, Vaughan DE, Morrow JD, and Brown NJ. Angiotensin II induces IL-6 in humans through a mineralocorticoid receptor-dependent mechanism. Hypertension. 2006; 48: 1050–1057.
Schieffer B, Schieffer E, Hilfiker-Kleiner D, Hilfiker A, Kovanen PT, Kaartinen M, Nussberger J, Harringer W, Drexler H. Expression of angiotensin II and IL 6 in human coronary atherosclerotic plaques: potential implications for inflammation and plaque instability. Circulation. 2000; 101: 1372–1378.
Manfredini R, Tenedini E, Siena M, Tagliafico E, Montanari M, Grande A, Zanocco-Marani T, Poligani C, Zini R, Gemelli C, Bergamaschi A, Vignudelli T, De Rienzo F, De Benedetti PG, Menziani MC, Ferrari S. Development of an IL-6 antagonist peptide that induces apoptosis in 7TD1 cells. Peptides. 2003; 24: 1207–1220.
Maini RN, Taylor PC, Szechinski J, Pavelka K, Broll J, Balint G, Emery P, Raemen F, Petersen J, Smolen J, Thomson D, Kishimoto T, and CHARISMA Study Group. Double-blind randomized controlled clinical trial of the IL-6 receptor antagonist, tocilizumab, in european patients with rheumatoid arthritis who had an incomplete response to methotrexate. Arthritis Rheum. 2006; 54: 2817–2829.