Interleukin-6 and Oligoclonal IgG Synthesis in Children with Acute Disseminated Encephalomyelitis

Abstract

Interleukin-6 (IL-6) has a number of roles including recruitment of T lymphocytes and differentiation of B lymphocytes into IgG-secreting plasma cells. Furthermore, IL-6 is a neuropoietic cytokine with effects on neuronal differentiation, function and survival. We studied IL-6 concentrations in children with acute disseminated encephalomyelitis (ADEM; n = 14), and compared the values with those obtained from control patients with other inflammatory (OIND; n = 13) and non-inflammatory (NIND; n = 10) neurological disorders. Patients with ADEM had a significantly increased CSF IL-6 concentration compared with both OIND and NIND groups (P < 0.01). Serum IL-6 was also increased in the ADEM group compared with the OIND group (P < 0.05). CSF: serum IL-6 ratios were significantly increased in the ADEM group compared with the NIND group (P < 0.05), suggesting an intrathecal production of IL-6 rather than its passive transfer across the blood-brain barrier alone. In ADEM, there was a significant correlation between an increased CSF IL-6 and an identical pattern of oligoclonal IgG synthesis in both serum and CSF (P < 0.05). These results would suggest a role for IL-6 in the pathology of ADEM, and a possible direct link between an increased IL-6 and a proliferation of B lymphocytes with consequent IgG production.

Key words

ADEM - antibody - demyelination - IL-6

References

• 1 Cserr H F, DePasquale M, Harling-Berg C J, Park J T, Knopf P M. Afferent and efferent arms of the humoral immune response to CSF-administered albumins in a rat model with normal blood-brain barrier permeability.  J Neuroimmunol. 1992;  41 195-202
• 2 Dale R C, de Sousa C, Chong W K, Cox T C, Harding B, Neville B G. Acute disseminated encephalomyelitis, multiphasic disseminated encephalomyelitis and multiple sclerosis in children.  Brain. 2000;  123 2407-2422
• 3 Dale R C, Church A J, Cardoso F, Goddard E, Cox T C, Chong W K. et al . Poststreptococcal acute disseminated encephalomyelitis with basal ganglia involvement and auto-reactive antibasal ganglia antibodies.  Ann Neurol. 2001;  50 588-595
• 4 Eeg-Olofsson O, Link H, Wigertz A. Concentrations of CSF proteins as a measure of blood brain barrier function and synthesis of IgG within the CNS in ‘normal’ subjects from the age of 6 months to 30 years.  Acta Paediatr Scand. 1981;  70 167-170
• 5 Eugster H P, Frei K, Kopf M, Lassmann H, Fontana A. IL-6-deficient mice resist myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis.  Eur J Immunol. 1998;  28 2178-2187
• 6 Gadient R A, Otten U H. Interleukin-6 (IL-6) - a molecule with both beneficial and destructive potentials.  Prog Neurobiol. 1997;  52 379-390
• 7 Gijbels K, Van Damme J, Proost P, Put W, Carton H, Billiau A. Interleukin 6 production in the central nervous system during experimental autoimmune encephalomyelitis.  Eur J Immunol. 1990;  20 233-235
• 8 Ichiyama T, Shoji H, Kato M, Sawaishi Y, Ozawa H, Matsubara T. et al . Cerebrospinal fluid levels of cytokines and soluble tumour necrosis factor receptor in acute disseminated encephalomyelitis.  Eur J Pediatr. 2002;  161 133-137
• 9 Jara L J, Irigoyen L, Ortiz M J, Zazueta B, Bravo G, Espinoza L R. Prolactin and interleukin-6 in neuropsychiatric lupus erythematosus.  Clin Rheumatol. 1998;  17 110-114
• 10 Jones S A, Rose-John S. The role of soluble receptors in cytokine biology: the agonistic properties of the sIL-6 R/IL-6 complex.  Biochim Biophys Acta. 2002;  1592 251-263
• 11 Jorens P G, VanderBorght A, Ceulemans B, Van Bever H P, Bossaert L L, Ieven M. et al . Encephalomyelitis-associated antimyelin autoreactivity induced by streptococcal exotoxins.  Neurology. 2000;  54 1433-1441
• 12 Knopf P M, Harling-Berg C J, Cserr H F, Basu D, Sirulnick E J, Nolan S C. et al . Antigen-dependent intrathecal antibody synthesis in the normal rat brain: tissue entry and local retention of antigen-specific B cells.  J Immunol. 1998;  161 692-701
• 13 Navikas V, Matusevicius D, Soderstrom M, Fredrikson S, Kivisakk P, Ljungdahl A. et al . Increased interleukin-6 mRNA expression in blood and cerebrospinal fluid mononuclear cells in multiple sclerosis.  J Neuroimmunol. 1996;  64 63-69
• 14 Pohl-Koppe A, Burchett S K, Thiele E A, Hafler D A. Myelin basic protein reactive Th2 T cells are found in acute disseminated encephalomyelitis.  J Neuroimmunol. 1998;  91 19-27
• 15 Roitt I M. The acquired immune response. Roitt IM Essential Immunology. 9th ed. Oxford, UK; Blackwell Science Ltd 185-187
• 16 Savman K, Blennow M, Gustafson K, Tarkowski E, Hagberg H. Cytokine response in cerebrospinal fluid after birth asphyxia.  Pediatr Res. 1998;  43 746-751