Interleukin 6: at the interface of human health and disease

Interleukin 6 (IL-6) is a pleiotropic cytokine executing a diverse number of functions, ranging from its effects on acute phase reactant pathways, B and T lymphocytes, blood brain barrier permeability, synovial inflammation, hematopoiesis, and embryonic development. This cytokine empowers the transition between innate and adaptive immune responses and helps recruit macrophages and lymphocytes to the sites of injury or infection. Given that IL-6 is involved both in the immune homeostasis and pathogenesis of several autoimmune diseases, research into therapeutic modulation of IL-6 axis resulted in the approval of a number of effective treatments for several autoimmune disorders like neuromyelitis optica spectrum disorder (NMOSD), rheumatoid arthritis, juvenile idiopathic arthritis, polyarticular juvenile idiopathic arthritis, giant cell arteritis (GCA), and cytokine release syndrome, associated with SARS-CoV2 pneumonia. This review discusses downstream inflammatory pathways of IL-6 expression and therapeutic applications of IL-6 blockade, currently investigated for the treatment of several other autoimmune conditions such as autoimmune encephalitis, autoimmune epilepsy, as well as myelin oligodendrocyte glycoprotein associated demyelination (MOGAD). This review further highlights the need for clinical trials to evaluate IL-6 blockade in disorders such neuropsychiatric lupus erythematosus (SLE), sarcoidosis and Behcet’s

Case report: Use of granulocyte-colony stimulating factor as an immunomodulatory therapy in a patient with neuromyelitis optica spectrum disorder and comorbid immunodeficiency

BackgroundAutoimmune diseases can coexist with immunodeficiency. We describe a treatment approach in which granulocyte-colony stimulating factor (G-CSF) is used to restore immune competence without worsening autoimmunity. G-CSF is a polyfunctional cytokine that influences survival, proliferation, and differentiation of hematopoietic stem cells, and has immunomodulatory effects on the innate and adaptive immune systems.ObjectiveTo report a case of neuromyelitis optica spectrum disorder (NMOSD) with comorbid immunodeficiency and frequent infections.MethodsCase report and review of literature.ResultsA 23 years-old man presented with a focal onset seizure with impaired awareness at age 12. At age 18, he developed headaches, recurrent multifocal seizures, and non-convulsive status epilepticus. Brain magnetic resonance imaging (MRI) showed extensive T2 hyperintense and gadolinium-enhancing periventricular and corpus callosum lesions. Serum aquaporin 4 antibody was positive 1:10,000 (normal value <1.5 titer), hence he was diagnosed with NMOSD. As a complication, patient developed mucormycotic pneumonia with cavitation, requiring thoracotomy precluding use of immunosuppressants. Gene testing demonstrated a mutation in MT-ND4 gene encoding for NADH dehydrogenase 4 in mitochondrial complex 1. Eventually, he began a treatment with filgrastim, a G-CSF analog, in addition to intravenous immunoglobulins and prednisone. Patient’s NMOSD has been in remission without relapses, or coexistent infections ever since.ConclusionG-CSF is a polyfunctional cytokine with important immunomodulatory effects, which makes it an interesting therapeutic option when autoimmunity coexists with immunodeficiency and was used successfully in this case

Selective and coherent activity increases due to stimulation indicate functional distinctions between episodic memory networks

Posterior-medial and anterior-temporal cortical networks interact with the hippocampus and are thought to distinctly support episodic memory. We causally tested this putative distinction by determining whether targeted noninvasive stimulation could selectively affect neural signals of memory formation within the posterior-medial network. Stimulation enhanced the posterior-medial network's evoked response to stimuli during memory formation, and this activity increase was coherent throughout the network. In contrast, there was no increase in anterior temporal network activity due to stimulation. In addition, control stimulation of an out-of-network prefrontal cortex location in a separate group of subjects did not influence memory-related activity in either network. The posterior-medial network is therefore a functional unit for memory processing that is distinct from the anterior temporal network. These findings suggest that targeted stimulation can lead to network-specific increases in excitability during memory formation and hold promise for efforts to fine-tune network involvement in episodic memory via brain stimulation © 2018 The Authors, some rights reserved

Early and persistent \u27extreme delta brush\u27 in a patient with anti-NMDA receptor encephalitis

Since its original description in 2007, anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis associated with an ovarian teratoma is an increasingly recognized etiology of previously unexplained encephalopathy and encephalitis. Extreme delta brush (EDB) is a novel electroencephalogram (EEG) finding seen in many patients with anti-NMDAR encephalitis. The presence of this pattern is associated with a more prolonged illness, although the specificity of this pattern is unclear. Additionally, the frequency and sensitivity of EDB in anti-NMDAR encephalitis and its implications for outcome have yet to be determined. We report a patient with early evidence of extreme delta brush and persistence of this pattern 17.5. weeks later with little clinical improvement. © 2014 The Authors

Early and persistent ‘extreme delta brush’ in a patient with anti-NMDA receptor encephalitis

Since its original description in 2007, anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis associated with an ovarian teratoma is an increasingly recognized etiology of previously unexplained encephalopathy and encephalitis. Extreme delta brush (EDB) is a novel electroencephalogram (EEG) finding seen in many patients with anti-NMDAR encephalitis. The presence of this pattern is associated with a more prolonged illness, although the specificity of this pattern is unclear. Additionally, the frequency and sensitivity of EDB in anti-NMDAR encephalitis and its implications for outcome have yet to be determined. We report a patient with early evidence of extreme delta brush and persistence of this pattern 17.5 weeks later with little clinical improvement

Data_Sheet_1_Case report: Use of granulocyte-colony stimulating factor as an immunomodulatory therapy in a patient with neuromyelitis optica spectrum disorder and comorbid immunodeficiency.PDF

BackgroundAutoimmune diseases can coexist with immunodeficiency. We describe a treatment approach in which granulocyte-colony stimulating factor (G-CSF) is used to restore immune competence without worsening autoimmunity. G-CSF is a polyfunctional cytokine that influences survival, proliferation, and differentiation of hematopoietic stem cells, and has immunomodulatory effects on the innate and adaptive immune systems.ObjectiveTo report a case of neuromyelitis optica spectrum disorder (NMOSD) with comorbid immunodeficiency and frequent infections.MethodsCase report and review of literature.ResultsA 23 years-old man presented with a focal onset seizure with impaired awareness at age 12. At age 18, he developed headaches, recurrent multifocal seizures, and non-convulsive status epilepticus. Brain magnetic resonance imaging (MRI) showed extensive T2 hyperintense and gadolinium-enhancing periventricular and corpus callosum lesions. Serum aquaporin 4 antibody was positive 1:10,000 (normal value ConclusionG-CSF is a polyfunctional cytokine with important immunomodulatory effects, which makes it an interesting therapeutic option when autoimmunity coexists with immunodeficiency and was used successfully in this case.</p

Supplementary Materials

Supplementary Material