Cyclosporin A as an Alternative Neuroimmune Strategy to Control Neurites and Recover Neuronal Tissues in Leprosy.

Leprosy, also known as Hansen's disease, continues to have a substantial impact on infectious diseases throughout the world. Leprosy is a chronic granulomatous infection caused by Mycobacterium leprae and shows a wide clinical and immunopathological spectrum related to the immune response of the host. This disease affects the skin and other internal organs with a predilection to infect Schwann cells, which play an active role during axonal degeneration, affecting peripheral nerves and promoting neurological damage. This chronic inflammation influences immune function, leading to neuroimmune disorders. Leprosy is also associated with neuroimmune reactions, including type 1 (reverse) and type 2 (erythema nodosum leprosum) reactions, which are immune-mediated inflammatory complications that can occur during the disease and appear to worsen dramatically; these complications are the main concerns of patients. The reactions may induce neuritis and neuropathic pain that progressively worsen with irreversible deformity and disabilities responsible for the immunopathological damage and glial/neuronal death. However, the neuronal damage is not always associated with the reactional episode. Also, the efficacy in the treatment of reactions remains low because of the nonexistence of a specific treatment and missing informations about the immunopathogenesis of the reactional episode. There is increasing evidence that peripheral neuron dysfunction strongly depends on the activity of neurotrophins. The most important neurotrophin in leprosy is nerve growth factor (NGF), which is decreased in the course of leprosy, as well as the presence of autoantibodies against NGF in all clinical forms of leprosy and neuroimmune reactions. The levels of autoantibodies against NGF are decreased by the immunomodulatory activity of cyclosporin A, which mainly controls pain and improves motor function and sensitivity. Therefore, the suppression of anti-NGF and the regulation of NGF levels can be attractive targets for immunomodulatory treatment and for controlling the neuroimmune reactions of leprosy, although further studies are needed to clarify this point.

Cyclosporine A treatment of leprosy patients with chronic neuritis is associated with pain control and reduction in antibodies against nerve growth factor.

OBJECTIVES: Chronic neuritis (CN) is still a major problem in leprosy and is difficult to manage in patients who do not respond well to prednisone. In this study we (i) evaluate the efficacy of cyclosporine A (CyA) in controlling CN patients, and (ii) analyse the presence of anti-NGF antibodies in the sera of leprosy patients, and their behaviour during CyA treatment. DESIGN: This was an open, prospective, non-comparative study. Sixty-seven leprosy patients in three different institutions in Pará, Brazil were studied from January, 2001 to January, 2004. Of these, 47 had no CN and 20 were leprosy patients suffering from CN and taking at least 40 mg/day prednisone to control nerve impairment and pain. Patients received 12 months reducing course CyA starting at 5 mg/kg per day. The outcome measure was sensory impairment, assessed using Semmes-Weinstein monofilament examination (SWME), muscular force and spontaneous or palpation-related pain. RESULTS: Antibodies against NGF were detected in the sera of leprosy patients, which may explain the depletion of NGF in leprosy contributing to neuritis, inflammation and loss of cutaneous nociception. The levels of these antibodies in CN patients were slightly lower than in patients with no CN. However, anti-NGF titres in CN patients treated with CyA were lowered to levels similar to those in the normal subjects. There was also improvement in sensory impairment, muscular force and pain. CONCLUSIONS: These data suggest that anti-NGF antibodies are present in the sera of leprosy patients and may influence the outcome of neuritis, and that CyA might be a useful drug in controlling nerve impairment and pain in leprosy patients.