title: Immunohistochemical analysis of the expression of TNF-alpha, TGF-beta, and caspase-3 in subcutaneous tissue of patients with HIV lipodystrophy syndrome.
abstract: BACKGROUND
  HIV Lipodystrophy Syndrome (HIVLS) is a multifactorial clinical expression that presents alterations in the metabolism and distribution pattern of body fat via immunological changes capable of disrupting homeostasis. This study aimed to analyze the degree of inflammatory, anti-inflammatory, and apoptosis activity in the subcutaneous tissue of patients, based on the expression of Tumor Necrosis Factor-α (TNF-α), Transforming Growth Factor-β (TGF-β), and caspase-3, respectively, and correlate them with clinical data and with each other.
  
  
  METHODS
  This is a cross-analytical study. The biopsy of subcutaneous cellular tissue was performed on the right thigh of 19 patients with HIVLS who were attended to at a university hospital, and four people without HIV and lipodystrophy, for comparison. The type of lipodystrophy and the estimation of body fat were obtained during the consultation or obtained from medical charts. The cytokine expression was observed in the adipose tissue through the streptavidin-biotin peroxidase method, and analyzed by optical microscopy.
  
  
  RESULTS
  Despite the mixed clinical form having been prevalent in both genders, men were more lipoatrophic and women were more lipohypertrophic. Men showed higher expression of TNF-α and caspase-3 than women. Patients with lipodystrophy had higher expression of TNF-α and caspase-3 and lower TGF-β, compared to the control group. The percentage of body fat was negatively correlated with the expression of TNF-α and caspase-3. Longer durations of infection and use of antiretroviral therapy (ARVT) were positively associated with the levels of TNF-α. The expression of caspase-3 and TGF-β was associated with higher levels of TNF-α.
  
  
  CONCLUSIONS
  Regardless of the clinical form, HIVLS is characterized by a chronic inflammatory process associated with the male gender, the percentage of body fat, and lipoatrophy manifestations. There is increased apoptotic activity in more inflamed tissues and there is correlation between TNF-α and TGF-β, which suggests a possible negative feedback mechanism between the inflammatory and anti-inflammatory activity.
authors.affiliation: Lipodystrophy Clinic, João de Barros Barreto University Hospital, Faculty of Medicine, Federal University of Pará (UFPA), Rua dos Mundurucus 4487, 66073-000 Belém, Pará, Brazil; Laboratory of Immunology, Center for Tropical Medicine, Federal University of Pará (UFP), Avenida Generalíssimo Deodoro 92, 66055-240 Belém, Pará, Brazil.
authors.forename: Sandro Henrique
authors.initials: SH
authors.lastname: de Souza Dantas Oliveira
authors.affiliation: Laboratory of Immunology, Center for Tropical Medicine, Federal University of Pará (UFP), Avenida Generalíssimo Deodoro 92, 66055-240 Belém, Pará, Brazil.
authors.forename: Tinara Leila
authors.initials: TL
authors.lastname: de Souza Aarão
authors.affiliation: Lipodystrophy Clinic, João de Barros Barreto University Hospital, Faculty of Medicine, Federal University of Pará (UFPA), Rua dos Mundurucus 4487, 66073-000 Belém, Pará, Brazil.
authors.forename: Leonardo
authors.initials: L
authors.lastname: da Silva Barbosa
authors.affiliation: Lipodystrophy Clinic, João de Barros Barreto University Hospital, Faculty of Medicine, Federal University of Pará (UFPA), Rua dos Mundurucus 4487, 66073-000 Belém, Pará, Brazil.
authors.forename: Paulo Guilherme
authors.initials: PG
authors.lastname: Souza Lisbôa
authors.affiliation: Lipodystrophy Clinic, João de Barros Barreto University Hospital, Faculty of Nutrition, Federal University of Pará (UFPA), Rua Augusto Corrêa 01, 66075-110 Belém, Pará, Brazil.
authors.forename: Claudia Daniele
authors.initials: CD
authors.lastname: Tavares Dutra
authors.affiliation: Lipodystrophy Clinic, João de Barros Barreto University Hospital, Faculty of Medicine, Federal University of Pará (UFPA), Rua dos Mundurucus 4487, 66073-000 Belém, Pará, Brazil.
authors.forename: Lorena
authors.initials: L
authors.lastname: Margalho Sousa
authors.affiliation: Laboratory of Immunology, Center for Tropical Medicine, Federal University of Pará (UFP), Avenida Generalíssimo Deodoro 92, 66055-240 Belém, Pará, Brazil.
authors.forename: Juarez Antônio
authors.initials: JA
authors.lastname: Simões Quaresma
authors.affiliation: Lipodystrophy Clinic, João de Barros Barreto University Hospital, Faculty of Medicine, Federal University of Pará (UFPA), Rua dos Mundurucus 4487, 66073-000 Belém, Pará, Brazil; Laboratory of Immunology, Center for Tropical Medicine, Federal University of Pará (UFP), Avenida Generalíssimo Deodoro 92, 66055-240 Belém, Pará, Brazil. Electronic address: rosanalibonati@terra.com.br.
authors.forename: Rosana Maria
authors.initials: RM
authors.lastname: Feio Libonati
mesh_terms: D000328:Adult; D017209:Apoptosis; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D039682:HIV-Associated Lipodystrophy Syndrome / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007120:Immunochemistry; D008297:Male; D008875:Middle Aged; D040521:Subcutaneous Tissue / Q000378:metabolism* / Q000503:physiopathology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D053148:Caspase 3
keywords: Caspase 3; Etiology; HIV Lipodystrophy Syndrome; Transforming Growth factor beta; Tumor necrosis factor alpha