title: Increase in cholinergic modulation with pyridostigmine induces anti-inflammatory cell recruitment soon after acute myocardial infarction in rats.
abstract: We tested the hypothesis that an increase in the anti-inflammatory cholinergic pathway, when induced by pyridostigmine (PY), may modulate subtypes of lymphocytes (CD4+, CD8+, FOXP3+) and macrophages (M1/M2) soon after myocardial infarction (MI) in rats. Wistar rats, randomly allocated to receive PY (40 mg·kg(-1)·day(-1)) in drinking water or to stay without treatment, were followed for 4 days and then were subjected to ligation of the left coronary artery. The groups-denominated as the pyridostigmine-treated infarcted (IP) and infarcted control (I) groups-were submitted to euthanasia 3 days after MI; the heart was removed for immunohistochemistry, and the peripheral blood and spleen were collected for flow cytometry analysis. Noninfarcted and untreated rats were used as controls (C Group). Echocardiographic measurements were registered on the second day after MI, and heart rate variability was measured on the third day after MI. The infarcted groups had similar MI areas, degrees of systolic dysfunction, blood pressures, and heart rates. Compared with the I Group, the IP Group showed a significant higher parasympathetic modulation and a lower sympathetic modulation, which were associated with a small, but significant, increase in diastolic function. The IP Group showed a significant increase in M2 macrophages and FOXP3(+)cells in the infarcted and peri-infarcted areas, a significantly higher frequency of circulating Treg cells (CD4(+)CD25(+)FOXP3(+)), and a less extreme decrease in conventional T cells (CD25(+)FOXP3(-)) compared with the I Group. Therefore, increasing cholinergic modulation with PY induces greater anti-inflammatory cell recruitment soon after MY in rats.
authors.affiliation: Heart Institute (InCor)-Hypertension Unit, Medical School University of São Paulo, São Paulo, Brazil.
authors.forename: Juraci Aparecida
authors.initials: JA
authors.lastname: Rocha
authors.affiliation: University of São Paulo-Medical School University of São Paulo, Laboratory of Clinical Immunology and Allergy, Division of Medicine, São Paulo, Brazil.
authors.forename: Susan Pereira
authors.initials: SP
authors.lastname: Ribeiro
authors.affiliation: University Nove de Julho, São Paulo, Brazil.
authors.forename: Cristiane Miranda
authors.initials: CM
authors.lastname: França
authors.affiliation: University Nove de Julho, São Paulo, Brazil.
authors.forename: Otávio
authors.initials: O
authors.lastname: Coelho
authors.affiliation: University Nove de Julho, São Paulo, Brazil.
authors.forename: Gisele
authors.initials: G
authors.lastname: Alves
authors.affiliation: Biomedical Sciences Institute, University of São Paulo, São Paulo, Brazil.
authors.forename: Silvia
authors.identifier: http://orcid.org/0000-0002-7937-8473
authors.initials: S
authors.lastname: Lacchini
authors.affiliation: University of São Paulo-Medical School University of São Paulo, Laboratory of Clinical Immunology and Allergy, Division of Medicine, São Paulo, Brazil.
authors.forename: Esper Georges
authors.initials: EG
authors.lastname: Kallás
authors.affiliation: Heart Institute (InCor)-Hypertension Unit, Medical School University of São Paulo, São Paulo, Brazil.
authors.forename: Maria Cláudia
authors.initials: MC
authors.lastname: Irigoyen
authors.affiliation: Heart Institute (InCor)-Hypertension Unit, Medical School University of São Paulo, São Paulo, Brazil University Nove de Julho, São Paulo, Brazil fernanda.consolim@incor.com.br.
authors.forename: Fernanda M
authors.initials: FM
authors.lastname: Consolim-Colombo
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D059329:Cholinergic Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D011729:Pyridostigmine Bromide / Q000494:pharmacology*; D011921:Rats, Inbred WKY; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D002800:Cholinesterase Inhibitors; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D011729:Pyridostigmine Bromide
keywords: T lymphocytes; anticholinesterase drugs; cholinergic anti-inflammatory reflex; macrophage activation; myocardial infarction