IL-6 and NMO

Interleukin-6 analysis of 572 consecutive CSF samples from neurological disorders: A special focus on neuromyelitis optica.

Crystal structure of IL-6
( protein data bank)

Uzawa A1, Mori M2, Masuda H2, Ohtani R2, Uchida T2, Sawai S3, Kuwabara S2.

Clin Chim Acta. 2017 Mar 7. pii: S0009-8981(17)30080-3. doi: 10.1016/j.cca.2017.03.006. [Epub ahead of print]

https://www.ncbi.nlm.nih.gov/pubmed/28283439#

Abstract

BACKGROUND: Increases of cerebrospinal fluid (CSF) interleukin (IL)-6 has been reported in various neurological disorders but has never been systematically analyzed. We compared the CSF IL-6 concentrations among various neurological disorders and to evaluate the significance of CSF IL-6 measurements for the diagnosis of neuromyelitis optica (NMO).

METHODS: We retrospectively investigated the IL-6 concentrations of 572 consecutive CSF samples in patients with various neurological disorders. Additionally, the associations between clinical manifestations in NMO patients and CSF IL-6 concentrations were closely investigated.

RESULTS: Among the neurological disorders, patients with NMO had the highest CSF IL-6 concentration. Receiver operating characteristic analysis found the optimal cutoff CSF IL-6 value for diagnosing NMO as 7.8pg/ml, and the sensitivity and specificity were 0.7317 and 0.7694, respectively. In NMO, CSF IL-6 concentrations were correlated with the length of the spinal cord lesion and anti-aquaporin-4 antibody-positivity and decreased after treatment.

CONCLUSION: The practical application of CSF IL-6 measurements is useful in diagnosing neurological disorders, especially NMO.

IL-6 is an important inflammatory mediator, present in the inflammatory response to infections, as well as in autoimmune processes. At present, in the field of neurology, we are increasingly used and experienced in anti-IL-6 therapy (tocilizumab), especially in NMOsd (in cases of non-response in the control of inflammatory activity with Rituximab or an allergic reaction that prevents the continued use of anti-CD20 therapy).

This work from the Chiba University group (Japan) led by Dr. Akiyuki Uzawa is very interesting and valuable, given the number of patients assessed, the cutoff value to determine the sensitivity of the test for NMO, and help differentiation of other inflammatory pathologies of the CNS with the NMO (as well as differentiation between the acute presentation of events between NMO and MS)

As shown in the graph of the article,** in patients with NMO, the cutoff value of IL-6 in CSF was 7.8 pg / ml, with sensitivity of 0.7317 and specificity of 0.7694.

The conclusions of the analysis of IL-6 values in these different pathologies are:

• In patients with Multiple Sclerosis, there was no increase in IL-6 concentration in CSF (the diagnostic specificity between acute events between NMO-a and MS-a was 0.9252)

• IL-6 levels in CSF were related to spinal cord length lesion in NMO patients .

• Levels of IL-6 in CSF decrease after treatment in acute onset (corticoid / plasmapheresis)

• The measurement of IL-6 in CSF, could be an important biomarker in the differentiation between NMO and MS

**Proportion of patients with a CSF IL-6 level above the cutoff level in various neurological disorders. The cutoff CSF IL-6 concentration was defined as 7.8 pg/ml, which was calculated by the ROC analysis. The NMO-a group had the highest proportion of patients with a CSF IL-6 concentration above the cutoff concentration **Proporción de pacientes con un nivel de IL-6 del LCR superior al nivel de corte en diversos trastornos neurológicos. El punto de corte de la concentración de IL-6 en CSF  se definió como 7,8 pg / ml, que se calculó mediante el análisis de ROC. El grupo NMO-a tuvo la mayor proporción de pacientes con una concentración de IL-6 del LCR por encima de la concentración de corte La IL-6 es un mediador inflamatorio importante , presente en la respuesta inflamatoria a infecciones , así como en procesos auto-inmunes . En la actualidad , en el campo de neurología , cada vez tenemos mas uso y experiencia en la   terapia anti -IL-6  (tocilizumab), sobre todo en NMOsd ( en casos de falta de respuesta en el control de la actividad inflamatoria  con   Rituximab  o reacción alérgica que impide continuar con el uso de terapia anti-CD20) .  Este trabajo del grupo de la Universidad Chiba ( Japón ) liderado por el Dr Akiyuki Uzawa, es muy interesante y valioso , dado el numero de pacientes valorados , el valor de corte para determinar la sensibilidad de la prueba para NMO , y ayudar a la diferenciación de otras patologías inflamatorias del SNC con el NMO (así mismo diferenciación entre la presentación aguda de eventos entre NMO y MS )  Como vemos en la grafica del articulo**,  en pacientes con NMO , el valor de corte de IL-6 en el CSF , fue de 7.8 pg/ml, con sensibilidad de   0.7317 y especificidad de  0.7694. Las conclusiones del análisis de los valores de IL-6 en estas diferentes patologías es :  • En pacientes en Esclerosis Multiple no se aprecia un incremento en la concentración de IL-6 en CSF (la especificidad de diagnostico entre los eventos agudos entre  NMO-a y MS-a fue del 0.9252) •  Los niveles de IL-6 en CSF  ,estuvieron relacionados con la longitud de lesion medular en pacientes con NMO . • Los niveles de Il-6 en CSF , disminuyen posterior al tratamiento , en la instauración aguda (corticoterapia / plasmaferesis )  • La medicion de IL-6 en CSF , podría ser un biomarcador importante en la diferenciación entre NMO y MS