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Vol. 32. Issue. 1.January 2012
Pages 1-132
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Vol. 32. Issue. 1.January 2012
Pages 1-132
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The role of interleukin 6 in the pathogenesis of hyponatremia associated with Guillain-Barré syndrome
Se Jin Parka, Ki Soo Paia, Ji Hong Kimb, Jae II Shinb
a Department of Pediatrics, Ajou University School of Medicine, Ajou University, Suwon, Korea,
b Department of Pediatrics, Yonsei University College of Medicine, Severance Children¿s Hospital, Seoul, Korea,
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Dear Editor,

We read with great interest the contribution by Monzón et al.1 They reported a significant case of a man who had Guillain-Barré syndrome (GBS) with syndrome of inappropriate antidiuretic hormone (SIADH) and speculated that increased sensitivity to vasopressin in the renal tubule and a long-lasting hypo-osmolarity or antidiuretic substances might cause GBS-related SIADH. However, we would like to add a possible pathomechanism in the development of hyponatremia associated with GBS.

According to a previous study by Maimone et al.,2 interleukin (IL)-6, a multifunctional cytokine, might be implicated in the immunopathogenesis of GBS. In their study, serum IL-6 levels were increased in six (26%) of 23 GBS patients, and detectable levels of IL-6 were also found in the cerebrospinal fluid in 13 (57%).2 Using enzyme-linked immunospot assays, Press et al.3 found elevated numbers of IL-6-secreting blood mononuclear cells during the acute phase in patients with GBS.

Quite recently and importantly, Swart et al.4 depicted the cascade-like fashion of events initiated by an inflammatory stimulus (lipopolysaccharides), with tumor necrosis factor-α secreted first, IL-1β second, and IL-6 last, suggesting possible pathways connecting IL-6 to vasopressin release. These pro-inflammatory cytokines are secreted into the systemic circulation to initiate the acute phase response which is involved in the innate immune system.5

Furthermore, Mastorakos et al.6 reported that plasma antidiuretic hormone levels were elevated after IL-6 injection in cancer patients, suggesting that IL-6 activated the magnocellular ADH-secreting neurons and that it might be involved in SIADH. Activation of the subfornical organ and the organum vasculosum of the lamina terminalis by IL-6 could eventually lead to thirst and increased vasopressin secretion by neurons from the supraoptic nucleus and paraventricular nucleus.4 The combination of antidiuresis and increased water intake may result in hyponatremia.

Therefore, there is a possibility that IL-6 may play a central role in the pathogenesis of hyponatremia associated with GBS. However, further studies are necessary to elucidate if IL-6 crosses the blood-brain barrier (BBB), or whether lipopolysaccharides crosse the BBB and then increases IL-6 locally in the brain in the future.


Conflict of interest

The authors declare they have no potential conflicts of interest related to the contents of this article.

Monzón Vázquez T, Florit E, Marqués Vidas M, Rodríguez Cubillo B, Delgado Conde P, Barrientos Guzmán A. Syndrome of inappropriate antidiuretic hormone hypersecretion associated with Guillain-Barré syndrome. Nefrologia 2011;31:498-9. [Pubmed]
Maimone D, Annunziata P, Simone IL, Livrea P, Guazzi GC. Interleukin-6 levels in the cerebrospinal fluid and serum of patients with Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy. J Neuroimmunol 1993;47:55-61. [Pubmed]
Press R, Ozenci V, Kouwenhoven M, Link H. Non-T(H)1 cytokines are augmented systematically early in Guillain-Barré syndrome. Neurology 2002;58:476-8. [Pubmed]
Swart RM, Hoorn EJ, Betjes MG, Zietse R. Hyponatremia and inflammation: the emerging role of interleukin-6 in osmoregulation. Nephron Physiol 2011;118:45-51. [Pubmed]
Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 1999;340:448-54. [Pubmed]
Mastorakos G, Weber JS, Magiakou MA, Gunn H, Chrousos GP. Hypothalamic-pituitary-adrenal axis activation and stimulation of systemic vasopressin secretion by recombinant interleukin-6 in humans: potential implications for the syndrome of inappropriate vasopressin secretion. J Clin Endocrinol Metab 1994;79:934-9. [Pubmed]
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