minocycline and Guillain-Barre-Syndrome

Topics: Adult; Aged; Anemia, Hemolytic; Anti-Bacterial Agents; Female; Guillain-Barre Syndrome; Humans; Japan; Lymphohistiocytosis, Hemophagocytic; Male; Middle Aged; Minocycline; Mycoplasma pneumoniae; Pneumonia, Mycoplasma; Steroids; Stevens-Johnson Syndrome; Young Adult

Experimental autoimmune neuritis (EAN) is a widely used animal model of the human acute inflammatory demyelinating polyradiculoneuropathy, which is the most common subtype of Guillain-Barré Syndrome. EAN is pathologically characterized by breakdown of the blood-nerve barrier, infiltration of reactive immune cells, local inflammation, demyelination in the peripheral nervous system and mechanical allodynia. Minocycline is known to have neuroprotective and anti-inflammatory effects. Furthermore, relieve of neuropathic pain following minocycline administration was observed in a variety of animal models. Here, we investigated the effects of minocycline on rat EAN. Suppressive treatment with minocycline (50 mg/kg body weight daily immediately after immunization) significantly attenuated the severity and duration of EAN. Macrophage and T-cell infiltration and demyelination in sciatic nerves of EAN rats treated with minocycline were significantly reduced compared to phosphate-buffered saline (PBS)-treated EAN rats. mRNA expressions of matrix metallopeptidase-9, inducible nitric oxide synthase and pro-inflammatory cytokines interleukin-1 beta and tumour necrosis factor-alpha in EAN sciatic nerves were greatly decreased by administration of minocycline as well. Furthermore, minocycline attenuated mechanical allodynia in EAN rats and greatly suppressed spinal microglial activation. All together, our data showed that minocycline could effectively suppress the peripheral and spinal inflammation (immune activation) to improve outcome in EAN rats, which suggests that minocycline may be considered as a potential candidate of pharmacological treatment for autoimmune-mediated neuropathies.

Topics: Animals; Anti-Bacterial Agents; Body Weight; Disease Models, Animal; Guillain-Barre Syndrome; Humans; Inflammation; Lymphocytes; Male; Matrix Metalloproteinase 9; Minocycline; Monocytes; Neuritis, Autoimmune, Experimental; Pain; Rats; Sciatic Nerve

Experimental autoimmune neuritis (EAN) is a well-known animal model of Guillain-Barré Syndrome. In this study, we studied the spatiotemporal expression of interleukin-16 (IL-16) in the nervous system of EAN rats and pharmacological effects of minocycline on IL-16 expressions in EAN rats. In sciatic nerves and dorsal/ventral roots of EAN rats, IL-16+ cells, identified as macrophages and T cells, were mainly found to concentrate around blood vessels. However, in spinal cords, IL-16+ microglial cells were mainly found in lumbar dorsal horns. Massive IL-16+ cell accumulation in sciatic nerves and spinal roots was temporally correlated with severity of neurological signs of EAN. Furthermore, a strong correlation of IL-16+ cell accumulation with local demyelination in perivascular areas of sciatic nerves, and significant reduction of IL-16+ cell numbers in sciatic nerves and spinal cords by minocycline suggested a pathological contribution of IL-16+ cells in EAN. Taken together, robust IL-16+ cell accumulation in the nervous system and its temporal correlation with severity of neurological signs in EAN might suggest a pathological role of IL-16 in EAN, which makes IL-16 a potential pharmacological target.

Topics: Animals; Disease Models, Animal; Guillain-Barre Syndrome; Immunohistochemistry; Interleukin-16; Macrophages; Male; Minocycline; Models, Statistical; Nerve Degeneration; Nerve Fibers, Myelinated; Neuritis, Autoimmune, Experimental; Neuroprotective Agents; Rats; Sciatic Nerve; Spinal Cord; Spinal Nerve Roots; T-Lymphocytes