title: The histopathological and immunological pattern of CBA mice infected with Leishmania amazonensis after treatment with pyrazole carbohydrazide derivatives.
abstract: Because there is no vaccine in clinical use, control of Leishmaniasis relies almost exclusively on chemotherapy and the conventional treatments exhibit high toxicity for patients and emerging drug resistance. Recently, we showed that oral treatment with synthetic pyrazole carbohydrazide compounds induced lower parasite load in draining lymph nodes and reduced skin lesion size without causing any toxic effects in an experimental murine infection model with Leishmania amazonensis. In this study, CBA mice were infected in the footpad with L. amazonensis and then orally treated with pyrazole carbohydrazides derivatives, such as BrNO(2), NO(2)Cl and NO(2)Br and their histopathological and immunological effects were then investigated. Epidermis and dermis had lower levels of inflammatory infiltration compared to the infected untreated control mice. In the dermis of treated animals, the numbers of vacuolated macrophages containing intracellular parasites were far lower than in infected untreated animals. In addition to dermal macrophages, we also observed a mixed inflammatory infiltrate containing lymphocytes and granulocyte cells. Lower numbers of B cells (B220+) and T lymphocytes (CD3+) were identified in the lesions of treated mice compared with the untreated, infected mice. In draining lymph node cells, the number of T lymphocytes (CD3+) was decreased, and the numbers of B cells (CD19+) and CD8+ T cells were increased in infected mice, when compared with the non-infected control group. In additional, we have shown that infected treated and untreated lymph node cells had similar levels of TGF-β and IFN-γ mRNA expression, whereas IL-4 was expressed at a lower level in the treated group. Increased levels of the specific anti-Leishmania IgG2a or IgG3 antibody subclass were observed in NO(2)Cl or BrNO(2)-treated group, respectively. Overall, our experimental findings suggest that pyrazole carbohydrazides exert modulation of IL-4 expression and B cell levels; however, further evaluation is required to determine the optimal treatment regime.
authors.affiliation: Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, RJ, Brazil.
authors.forename: Karen S
authors.initials: KS
authors.lastname: Charret
authors.forename: Jussara
authors.initials: J
authors.lastname: Lagrota-Cândido
authors.forename: Carla E
authors.initials: CE
authors.lastname: Carvalho-Pinto
authors.forename: Cristiane F
authors.initials: CF
authors.lastname: Hottz
authors.forename: Marie-Luce F
authors.initials: ML
authors.lastname: Lira
authors.forename: Raquel F
authors.initials: RF
authors.lastname: Rodrigues
authors.forename: Adriana O
authors.initials: AO
authors.lastname: Gomes
authors.forename: Alice M
authors.initials: AM
authors.lastname: Bernardino
authors.forename: Marilene M
authors.initials: MM
authors.lastname: Canto-Cavalheiro
authors.forename: Leonor L
authors.initials: LL
authors.lastname: Leon
authors.forename: Veronica F
authors.initials: VF
authors.lastname: Amaral
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006834:Hydrazines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D007150:Immunohistochemistry; D007894:Leishmania mexicana / Q000187:drug effects / Q000276:immunology / Q000472:pathogenicity*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000473:pathology; D008214:Lymphocytes / Q000145:classification / Q000166:cytology; D008264:Macrophages / Q000166:cytology / Q000469:parasitology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000469:parasitology / Q000473:pathology
chemical_list: D000913:Antibodies, Protozoan; D016207:Cytokines; D006834:Hydrazines; D007074:Immunoglobulin G; D011720:Pyrazoles; D012333:RNA, Messenger; C019289:carbohydrazide