Insulin-like growth factor-I serum levels and their biological effects on Leishmania isolates from different clinical forms of American tegumentary leishmaniasis.
American tegumentary leishmaniasis (ATL) in Brazil is mostly caused by Leishmania (Viannia) braziliensis, with known forms of the disease being cutaneous (CL), mucosal (ML) and disseminated (DL) leishmaniasis. The development of the lesion in ATL is related both to the persistence of the Leishmania in the skin and to the parasite-triggered immune and inflammatory responses that ensue lesions. In this context one factor with expected role in the pathogenesis is insulin-like growth factor (IGF)-I with known effects on parasite growth and healing and inflammatory processes. In the present study, we addressed the effect of IGF-I on intracellular amastigote isolates from CL, ML and DL patients within human macrophage and we evaluated the IGF-I and IGF-binding protein-3 (IGFBP3) serum levels in patients presenting different clinical forms and controls from the endemic area.



We evaluated biological variability in the responses of intracellular amastigotes of Leishmania isolates derived from CL, ML, and DL patients from an area for ATL in response to IGF-I. Intracellular amastigote growth was evaluated using the human macrophage cell line THP-1. Arginase activity in infected cells was evaluated quantifying the generated urea concentration. Serum samples from patients and controls were assayed using chemiluminescent immunometric assay to determine IGF-I and IGFBP3 levels.



We observed an increase in intracellular parasitism upon IGF-I stimulus in 62.5 % of isolates from CL, in 85.7 % from ML and only 42.8 % from DL cases. In DL, the basal arginase activity was lower than that of CL. We then evaluated the IGF-I and IGFBP3 serum levels in patients, and we observed significantly lower levels in ML and DL than in CL and control samples.



The data suggest that IGF-I is modulated distinctly in different clinical forms of tegumentary leishmaniasis. IGF-I seemingly exerts effect on parasite growth likely contributing to its persistence in the skin in earlier phase. In addition the decreased IGF-I serum levels may affect the modulation of inflammation and lesion healing in chronic phase. In view of potential role of IGF-I in the pathogenesis of ATL we can speculate on therapeutic procedures taking into account the local IGF-I level.
Laboratório de Soroepidemiologia e Imunobiologia, Instituto de Medicina Tropical de São Paulo, Universidade de São Paulo, Avenida Dr. Enéas de Carvalho Aguiar n 470, prédio II, 4 andar, CEP 05403-000, São Paulo, SP, Brazil.
Luana Dias
LD
de Souza
Laboratório de Soroepidemiologia e Imunobiologia, Instituto de Medicina Tropical de São Paulo, Universidade de São Paulo, Avenida Dr. Enéas de Carvalho Aguiar n 470, prédio II, 4 andar, CEP 05403-000, São Paulo, SP, Brazil.|Serviço de Imunologia, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brazil.
Célia Maria Vieira
CM
Vendrame
Laboratório de Biologia Molecular, Departamento de Medicina Interna e Patologia, Universidade Federal de Sergipe, Aracaju, SE, Brazil.
Amélia Ribeiro
AR
de Jesus
Laboratório de Soroepidemiologia e Imunobiologia, Instituto de Medicina Tropical de São Paulo, Universidade de São Paulo, Avenida Dr. Enéas de Carvalho Aguiar n 470, prédio II, 4 andar, CEP 05403-000, São Paulo, SP, Brazil.
Márcia Dias Teixeira
MD
Carvalho
Serviço de Imunologia, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brazil.
Andréa Santos
AS
Magalhães
Serviço de Imunologia, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brazil.
Albert
A
Schriefer
Serviço de Imunologia, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brazil.
Luiz Henrique
LH
Guimarães
Serviço de Imunologia, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brazil.
Edgar Marcelino de
EM
Carvalho
Laboratório de Soroepidemiologia e Imunobiologia, Instituto de Medicina Tropical de São Paulo, Universidade de São Paulo, Avenida Dr. Enéas de Carvalho Aguiar n 470, prédio II, 4 andar, CEP 05403-000, São Paulo, SP, Brazil. hgoto@usp.br.|Departamento de Medicina Preventiva, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, SP, Brazil. hgoto@usp.br.
Hiro
H
Goto
D000328:Adult; D000368:Aged; D002460:Cell Line; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D007891:Leishmania / Q000187:drug effects*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000469:parasitology*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I
IGF-I level; Leishmania braziliensis; THP-1; Tegumentary leishmaniasis