Regulation of murine arthritis by systemic,spinal, and intra-articular adrenoceptors |
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Authors: | Alexandre Kanashiro Thais Oliveira de Lucena Leoncio Ayda Henriques Schneider Hélio Rocha Alves Gabriel Shimizu Bassi Sabrina Graziani Veloso Dutra Fernando de Queiróz Cunha Luis Ulloa David do Carmo Malvar |
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Institution: | 1. Department of Physiological Sciences, Federal Rural University of Rio de Janeiro, Seropédica, RJ, Brazil;2. Department of Neurosciences and Behavior, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil;3. Department of Surgery, Center of Immunology and Inflammation, Rutgers University - New Jersey Medical School, Newark, NJ, USA;4. Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil |
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Abstract: | BackgroundThe regulation of the immune system by the sympathetic nervous system is allowing the design of novel treatments for inflammatory disorders such as arthritis. In this study, we have analyzed the effects of α- and β-adrenoceptor agonists injected subcutaneously, intrathecally, or intra-articularly in zymosan-induced arthritis.MethodsMurine arthritis was induced by intra-articular (knee joint) injection of zymosan. α1 (phenylephrine), α2 (clonidine), β1 (dobutamine), or β2 (salbutamol)-adrenoceptor agonists were injected subcutaneously (sc), intrathecally (it), or intra-articularly (ia) to activate peripheral, spinal, or intra-articular adrenoceptors and to study their effects on articular edema formation and neutrophil migration into the synovial cavity.ResultsTreatments with phenylephrine did not affect the edema formation, but it increased neutrophil migration when injected subcutaneously (155.3%) or intra-articularly (187.7%). Treatments with clonidine inhibited neutrophil migration (59.9% sc, 68.7% it, 42.8% ia) regardless of the route of administration, but it inhibited edema formation only when injected intrathecally (66.7%) or intra-articularly (36%) but not subcutaneously. Treatments with dobutamine inhibited both edema (42.0% sc, 69.5% it, 61.6% ia) and neutrophil migration (28.4% sc, 70.3% it, 82.4% ia) in a concentration dependent manner. Likewise, all the treatments with salbutamol also inhibited edema formation (89.9% sc, 62.4% it, 69.8% ia) and neutrophil migration (76.6% sc, 39.1% it, 71.7% ia).ConclusionWhereas the β-adrenoceptor agonists induced anti-inflammatory effects regardless of their route of administration, α1- and α2-adrenoceptor agonists induced either pro- and anti-inflammatory effects, respectively. |
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Keywords: | Corresponding authors Adrenoceptors Arthritis Inflammation Neuroimmune interactions Neuroimmunomodulation |
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