title: Intranasal administration of perillyl alcohol activates peripheral and bronchus-associated immune system in vivo.
abstract: Perillyl alcohol (POH) presents antitumoral activity but clinical application is hampered by adverse effects following oral administration. This work aimed to verify the cytotoxic effect of intranasal POH administration in the histology of lung, liver, brain; the cellularity and function of peripheral and bronchoalveolar-associated immune system. C57 adult mice received 1-min inhalation with POH, vehicle 70 % ethanol or saline buffer, once (84 μg/day) or twice (164 μg/day) during five consecutive days, and were killed 72 h after treatment. Spleen, cervical and mesenteric lymph nodes were removed for (3)H-thymidine proliferation assay, leukocyte cellularity and flow cytometry analysis. Peripheral blood and bronchoalveolar lavage cells were collected to assess cellularity and immunoglobulin (IgA, IgM) levels. Intranasal POH did not alter body weight or liver, brain and lung morphology, but increased splenocyte and cervical lymph node cell proliferation, and IgM production without altering peripheral lymphocyte subsets. Treatment also increased the percentage of alveolar macrophages (83 %) and IgA-producing lymphocytes (15 %), a pattern characteristic of activated bronchoalveolar innate immune system. Intranasal administration of POH activated peripheral immune system and innate immunity of bronchus-associated lymphoid tissue, thus suggesting a possible role for POH as a chemotherapeutic drug also in pathological processes affecting the lung.
authors.affiliation: Laboratory of Cellular Pathology, Department of Cellular and Molecular Biology, Institute of Biology, Fluminense Federal University, Niteroi, Rio de Janeiro, 24020-141, Brazil.
authors.forename: Marcela
authors.initials: M
authors.lastname: D'Alincourt Salazar
authors.forename: Rafael Ferreira
authors.initials: RF
authors.lastname: da Silva
authors.forename: Clovis Orlando
authors.initials: CO
authors.lastname: Da Fonseca
authors.forename: Jussara
authors.initials: J
authors.lastname: Lagrota-Candido
authors.forename: Thereza
authors.initials: T
authors.lastname: Quirico-Santos
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D001980:Bronchi / Q000187:drug effects* / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured; D005260:Female; D007107:Immune System / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects; D007070:Immunoglobulin A / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D008171:Lung Diseases / Q000188:drug therapy* / Q000276:immunology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D039821:Monoterpenes / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000970:Antineoplastic Agents; D007070:Immunoglobulin A; D007075:Immunoglobulin M; D039821:Monoterpenes; C032208:perillyl alcohol