Oliveira JG, Novais FO, de Oliveira CI, da Cruz Junior AC, Campos LF, da Rocha AV, Boaventura V, Noronha A, Costa JM, Barral A, 2005. Polymerase chain reaction (PCR) is highly sensitive for diagnosis of mucosal leishmaniasis. Acta Trop 94: 55–59.
Rosa AC, Cuba CC, Vexenat A, Barreto AC, Marsden PD, 1988. Predominance of Leishmania braziliensis braziliensis in the regions of Tres Bracos and Corte de Pedra, Bahia, Brazil. Trans R Soc Trop Med Hyg 82: 409–410.
Barral A, Guerreiro J, Bomfim G, Correia D, Barral-Netto M, Carvalho EM, 1995. Lymphadenopathy as the first sign of human cutaneous infection by Leishmania braziliensis. Am J Trop Med Hyg 53: 256–259.
Gaafar A, Veress B, Permin H, Kharazmi A, Theander TG, el Hassan AM, 1999. Characterization of the local and systemic immune responses in patients with cutaneous leishmaniasis due to Leishmania major. Clin Immunol 91: 314–320.
Pompeu MM, Brodskyn C, Teixeira MJ, Clarencio J, Van Weyenberg J, Coelho IC, Cardoso SA, Barral A, Barral-Netto M, 2001. Differences in gamma interferon production in vitro predict the pace of the in vivo response to Leishmania amazonensis in healthy volunteers. Infect Immun 69: 7453–7460.
Antonelli LR, Dutra WO, Almeida RP, Bacellar O, Gollob KJ, 2004. Antigen specific correlations of cellular immune responses in human leishmaniasis suggests mechanisms for immunoregulation. Clin Exp Immunol 136: 341–348.
D'Oliveira A Jr, Machado P, Bacellar O, Cheng LH, Almeida RP, Carvalho EM, 2002. Evaluation of IFN-gamma and TNF-alpha as immunological markers of clinical outcome in cutaneous leishmaniasis. Rev Soc Bras Med Trop 35: 7–10.
Bacellar O, Lessa H, Schriefer A, Machado P, Ribeiro de Jesus A, Dutra WO, Gollob KJ, Carvalho EM, 2002. Up-regulation of Th1-type responses in mucosal leishmaniasis patients. Infect Immun 70: 6734–6740.
Bafica A, Oliveira F, Freitas LA, Nascimento EG, Barral A, 2003. American cutaneous leishmaniasis unresponsive to antimonial drugs: successful treatment using combination of N-methilglucamine antimoniate plus pentoxifylline. Int J Dermatol 42: 203–207.
Antonelli LR, Dutra WO, Almeida RP, Bacellar O, Carvalho EM, Gollob KJ, 2005. Activated inflammatory T cells correlate with lesion size in human cutaneous leishmaniasis. Immunol Lett 101: 226–230.
Reed SG, Badaro R, Masur H, Carvalho EM, Lorenco R, Lisboa A, Teixeira R, Johnson WD Jr, Jones TC, 1986. Selection of a skin test antigen for American visceral leishmaniasis. Am J Trop Med Hyg 35: 79–85.
Machado P, Araujo C, Da Silva AT, Almeida RP, D'Oliveira A Jr, Bittencourt A, Carvalho EM, 2002. Failure of early treatment of cutaneous leishmaniasis in preventing the development of an ulcer. Clin Infect Dis 34: E69–E73.
Llanos-Cuentas EA, Marsden PD, Lago L, Barreto AC, Cuba CC, Johnson WD, 1984. Human cutaneous leishmaniasis in Três Braços, Bahia-Brazil. An area of Leishmania braziliensis transmission. II. Cutaneous disease presentation and evolution. Rev Soc Bras Med Trop 17: 169–177.
Van de Kerkhof PC, Van Bergen B, Spruijt K, Kuiper JP, 1994. Age-related changes in wound healing. Clin Exp Dermatol 19: 369–374.
Castes M, Trujillo D, Rojas ME, Fernandez CT, Araya L, Cabrera M, Blackwell J, Convit J, 1993. Serum levels of tumor necrosis factor in patients with American cutaneous leishmaniasis. Biol Res 26: 233–238.
Da-Cruz AM, de Oliveira MP, De Luca PM, Mendonca SC, Coutinho SG, 1996. Tumor necrosis factor-alpha in human american tegumentary leishmaniasis. Mem Inst Oswaldo Cruz 91: 225–229.
Barral-Netto M, Badaro R, Barral A, Almeida RP, Santos SB, Badaro F, Pedral-Sampaio D, Carvalho EM, Falcoff E, Falcoff R, 1991. Tumor necrosis factor (cachectin) in human visceral leishmaniasis. J Infect Dis 163: 853–857.
Trengove NJ, Bielefeldt-Ohmann H, Stacey MC, 2000. Mitogenic activity and cytokine levels in non-healing and healing chronic leg ulcers. Wound Repair Regen 8: 13–25.
Lessa HA, Machado P, Lima F, Cruz AA, Bacellar O, Guerreiro J, Carvalho EM, 2001. Successful treatment of refractory mucosal leishmaniasis with pentoxifylline plus antimony. Am J Trop Med Hyg 65: 87–89.
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Cutaneous leishmaniasis (CL) is a worldwide disease endemic in several regions of the globe. The hallmark of CL is skin ulcers likely driven by efforts of the immune system to control Leishmania growth. Cytokines, such as tumor necrosis factor (TNF) and interferon-gamma can control disease progression in animal models. Nevertheless, the impact of these cytokines in CL ulcer outcome is not well established in humans. In this study, 96 CL patients from an endemic area of Leishmania braziliensis were enrolled for a follow-up study that consisted of clinical and immunological evaluations in a 2-year period. Statistical analysis revealed that healing time (P = 0.029), age (P = 0.002), and TNF levels (P = 0.0002) positively correlate with ulcer size at the time of the first clinical evaluation. Our findings suggest that ulcer size correlates with healing time and TNF levels support the use of TNF inhibitors combined with standard therapy to improve healing in CL patients with severe lesions.
Financial support: This work is supported by grants from CNPq, FAPESB, and PAPES/FIOCRUZ. ABafica, JC, ABarral and MB-N are investigators from the Brazilian National Council for Scientific and Technological Development (CNPq).
Authors' addresses: Fabiano Oliveira, Laboratory of Malaria and Vector Research, National Institutes of Health, Rockville, MD, E-mail: deepbahia@gmail.com. Andre Bafica, Universidade Federal de Santa Catarina, Departamento de Microbiologia, Imunologia e Parasitologia, Florianopolis, Santa Catarina, Brazil, E-mail: abafica@ccb.ufsc.br. Andrea B. Rosato, Laboratório de Imunoparasitologia (LIP), Centro de Pesquisas Gonçalo Moniz (CPqGM), Fundação Oswaldo Cruz – FIOCRUZ - Bahia, Salvador, Bahia, Brazil, E-mail: rosatoab@hotmail.com. Cecilia B. F. Favali, Universidade de BrasÃlia, Instituto de Ciencias Biologicas, Departamento de Biologia Celular, Brasilia, Distrito Federal, Brazil, E-mail: cfavali@unb.br. Jackson M. Cost, Laboratório de Imunoparasitologia (LIP), Centro de Pesquisas Gonçalo Moniz (CPqGM), Fundação Oswaldo Cruz – FIOCRUZ - Bahia, Salvador, Bahia, Brazil, E-mail: jcosta@bahia.fiocruz.br. Virgina Cafe, Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Bahia, Brazil, E-mail: Vcafe@ufba.br. Manoel Barral-Netto, Laboratório de Imuno-regulação (LIMI), Centro de Pesquisas Gonçalo Moniz (CPqGM), Fundação Oswaldo Cruz – FIOCRUZ - Bahia, Salvador, Bahia, Brazil; Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Bahia, Brazil; and Instituto Nacional de Ciência e Tecnologia de Investigação em Imunologia - iii - INCT, Salvador, Bahia, Brazil, E-mail: manoel.barral@gmail.com. Aldina Barral, Laboratório de Imunoparasitologia (LIP), Centro de Pesquisas Gonçalo Moniz (CPqGM), Fundação Oswaldo Cruz – FIOCRUZ - Bahia, Salvador, Bahia, Brazil; Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Bahia, Brazil; and Instituto Nacional de Ciência e Tecnologia de Investigação em Imunologia - iii - INCT, Salvador, Bahia, Brazil, E-mail: abarral@bahia.fiocruz.br.
Oliveira JG, Novais FO, de Oliveira CI, da Cruz Junior AC, Campos LF, da Rocha AV, Boaventura V, Noronha A, Costa JM, Barral A, 2005. Polymerase chain reaction (PCR) is highly sensitive for diagnosis of mucosal leishmaniasis. Acta Trop 94: 55–59.
Rosa AC, Cuba CC, Vexenat A, Barreto AC, Marsden PD, 1988. Predominance of Leishmania braziliensis braziliensis in the regions of Tres Bracos and Corte de Pedra, Bahia, Brazil. Trans R Soc Trop Med Hyg 82: 409–410.
Barral A, Guerreiro J, Bomfim G, Correia D, Barral-Netto M, Carvalho EM, 1995. Lymphadenopathy as the first sign of human cutaneous infection by Leishmania braziliensis. Am J Trop Med Hyg 53: 256–259.
Gaafar A, Veress B, Permin H, Kharazmi A, Theander TG, el Hassan AM, 1999. Characterization of the local and systemic immune responses in patients with cutaneous leishmaniasis due to Leishmania major. Clin Immunol 91: 314–320.
Pompeu MM, Brodskyn C, Teixeira MJ, Clarencio J, Van Weyenberg J, Coelho IC, Cardoso SA, Barral A, Barral-Netto M, 2001. Differences in gamma interferon production in vitro predict the pace of the in vivo response to Leishmania amazonensis in healthy volunteers. Infect Immun 69: 7453–7460.
Antonelli LR, Dutra WO, Almeida RP, Bacellar O, Gollob KJ, 2004. Antigen specific correlations of cellular immune responses in human leishmaniasis suggests mechanisms for immunoregulation. Clin Exp Immunol 136: 341–348.
D'Oliveira A Jr, Machado P, Bacellar O, Cheng LH, Almeida RP, Carvalho EM, 2002. Evaluation of IFN-gamma and TNF-alpha as immunological markers of clinical outcome in cutaneous leishmaniasis. Rev Soc Bras Med Trop 35: 7–10.
Bacellar O, Lessa H, Schriefer A, Machado P, Ribeiro de Jesus A, Dutra WO, Gollob KJ, Carvalho EM, 2002. Up-regulation of Th1-type responses in mucosal leishmaniasis patients. Infect Immun 70: 6734–6740.
Bafica A, Oliveira F, Freitas LA, Nascimento EG, Barral A, 2003. American cutaneous leishmaniasis unresponsive to antimonial drugs: successful treatment using combination of N-methilglucamine antimoniate plus pentoxifylline. Int J Dermatol 42: 203–207.
Antonelli LR, Dutra WO, Almeida RP, Bacellar O, Carvalho EM, Gollob KJ, 2005. Activated inflammatory T cells correlate with lesion size in human cutaneous leishmaniasis. Immunol Lett 101: 226–230.
Reed SG, Badaro R, Masur H, Carvalho EM, Lorenco R, Lisboa A, Teixeira R, Johnson WD Jr, Jones TC, 1986. Selection of a skin test antigen for American visceral leishmaniasis. Am J Trop Med Hyg 35: 79–85.
Machado P, Araujo C, Da Silva AT, Almeida RP, D'Oliveira A Jr, Bittencourt A, Carvalho EM, 2002. Failure of early treatment of cutaneous leishmaniasis in preventing the development of an ulcer. Clin Infect Dis 34: E69–E73.
Llanos-Cuentas EA, Marsden PD, Lago L, Barreto AC, Cuba CC, Johnson WD, 1984. Human cutaneous leishmaniasis in Três Braços, Bahia-Brazil. An area of Leishmania braziliensis transmission. II. Cutaneous disease presentation and evolution. Rev Soc Bras Med Trop 17: 169–177.
Van de Kerkhof PC, Van Bergen B, Spruijt K, Kuiper JP, 1994. Age-related changes in wound healing. Clin Exp Dermatol 19: 369–374.
Castes M, Trujillo D, Rojas ME, Fernandez CT, Araya L, Cabrera M, Blackwell J, Convit J, 1993. Serum levels of tumor necrosis factor in patients with American cutaneous leishmaniasis. Biol Res 26: 233–238.
Da-Cruz AM, de Oliveira MP, De Luca PM, Mendonca SC, Coutinho SG, 1996. Tumor necrosis factor-alpha in human american tegumentary leishmaniasis. Mem Inst Oswaldo Cruz 91: 225–229.
Barral-Netto M, Badaro R, Barral A, Almeida RP, Santos SB, Badaro F, Pedral-Sampaio D, Carvalho EM, Falcoff E, Falcoff R, 1991. Tumor necrosis factor (cachectin) in human visceral leishmaniasis. J Infect Dis 163: 853–857.
Trengove NJ, Bielefeldt-Ohmann H, Stacey MC, 2000. Mitogenic activity and cytokine levels in non-healing and healing chronic leg ulcers. Wound Repair Regen 8: 13–25.
Lessa HA, Machado P, Lima F, Cruz AA, Bacellar O, Guerreiro J, Carvalho EM, 2001. Successful treatment of refractory mucosal leishmaniasis with pentoxifylline plus antimony. Am J Trop Med Hyg 65: 87–89.
Past two years | Past Year | Past 30 Days | |
---|---|---|---|
Abstract Views | 325 | 263 | 9 |
Full Text Views | 571 | 10 | 0 |
PDF Downloads | 104 | 7 | 0 |