Skip to main content
Top
Published in: Archives of Dermatological Research 2/2014

01-03-2014 | Original Paper

Assessment of serum level of interleukin-1β and interleukin-12 in leprosy: impact of previous Bacillus Calmitte Guerin vaccination

Authors: Mohammed A. Sallam, Enas A. S. Attia, Marwa S. E. Soliman

Published in: Archives of Dermatological Research | Issue 2/2014

Login to get access

Abstract

Macrophages play an important role in attempt to eliminate mycobacteria, via production of cytokines, including interleukin-1, and interleukin-12. Bacillus Calmitte Guerin (BCG) vaccination, known to induce interleukin-1β in tuberculosis, was originally aimed at tuberculosis control, but it showed efficacy against leprosy. Our aim was to estimate serum levels of interleukin-1β and interleukin-12, in leprosy, and to assess the impact of previous BCG vaccination on their levels. Serum interleukin-1β and interleukin-12 p70 were estimated in 43 leprotic patients and 43 controls by enzyme-linked immunosorbent assay. Patients were grouped according to presence or absence of reactions, as well as bacillary load. Serum interleukin-1β was significantly higher in patients as compared to controls (p = 0.047), and was significantly different in patients’ groups (p = 0.036); with significantly higher level in multibacillary patients, both non reactional and with erythema nodosum leprosum, compared with paucibacillary/non reactional patients (p = 0.012 and 0.049 respectively). A statistically significant higher interleukin-1β was found in BCG vaccinated paucibacillary patients as compared to unvaccinated patients (p = 0.031). Significantly elevated interleukin-12 was present in patients as compared to controls (p < 0.001), with no statistically significant difference comparing patients’ groups. BCG vaccination showed stimulatory effect on monocytes only in the immunocompetent paucibacillary leprosy patients, as evidenced by higher Interleukin-1β in this group. Interleukin-1β was shown to have a pro-inflammatory role in multibacillary patients with or without erythema nodosum leprosum. Targeting interleukin-1β may be promising to control episodic refractory erythema nodosum leprosum. Interleukin-12 may be a general marker of active Mycobacterium leprae infection.
Literature
1.
go back to reference Abhimanyu, Mangangcha IR, Jha P, Arora K, Mukerji M, Banavaliker JN, Indian Genome Variation Consortium, Brahmachari V, Bose M (2011) Differential serum cytokine levels are associated with cytokine gene polymorphisms in north Indians with active pulmonary tuberculosis. Infect Genet Evol 11:1015–1022 Abhimanyu, Mangangcha IR, Jha P, Arora K, Mukerji M, Banavaliker JN, Indian Genome Variation Consortium, Brahmachari V, Bose M (2011) Differential serum cytokine levels are associated with cytokine gene polymorphisms in north Indians with active pulmonary tuberculosis. Infect Genet Evol 11:1015–1022
2.
go back to reference Beutler B, Cerami A (1986) Cachectin and tumor necrosis factor as two sides of the same biological coin. Nature 320:584–588PubMedCrossRef Beutler B, Cerami A (1986) Cachectin and tumor necrosis factor as two sides of the same biological coin. Nature 320:584–588PubMedCrossRef
4.
go back to reference Chan SH, Kobayashi M, Santoli D, Perussia B, Trinchieri G (1992) Mechanisms of IFN-γ induction by natural killer cell stimulatory factor (NKSF/IL-12) role of transcription and mRNA stability in the synergistic interaction between NKSF and IL-2. J Immunol 148:92–98PubMed Chan SH, Kobayashi M, Santoli D, Perussia B, Trinchieri G (1992) Mechanisms of IFN-γ induction by natural killer cell stimulatory factor (NKSF/IL-12) role of transcription and mRNA stability in the synergistic interaction between NKSF and IL-2. J Immunol 148:92–98PubMed
5.
go back to reference Cuevas J, Rodriguez-Peralto JL, Carrillo R, Contreras F (2007) Erythema nodosum leprosum: reactional leprosy. Semin Cutan Med Surg 26:126–130PubMedCrossRef Cuevas J, Rodriguez-Peralto JL, Carrillo R, Contreras F (2007) Erythema nodosum leprosum: reactional leprosy. Semin Cutan Med Surg 26:126–130PubMedCrossRef
6.
go back to reference Dahl KE, Shiratsuchi H, Hamilton BD, Ellner JJ, Toossi Z (1996) Selective induction of transforming growth factor beta in human monocytes by lipoarabinomannan of Mycobacterium tuberculosis. Infect Immun 64:399–405PubMedCentralPubMed Dahl KE, Shiratsuchi H, Hamilton BD, Ellner JJ, Toossi Z (1996) Selective induction of transforming growth factor beta in human monocytes by lipoarabinomannan of Mycobacterium tuberculosis. Infect Immun 64:399–405PubMedCentralPubMed
7.
go back to reference De Paula L, Passos IM, Da Silva RC (2010) Serum levels of inflammatory cytokines in leprosy patients. Retrovirology 7(Suppl 1):190CrossRef De Paula L, Passos IM, Da Silva RC (2010) Serum levels of inflammatory cytokines in leprosy patients. Retrovirology 7(Suppl 1):190CrossRef
8.
go back to reference Dhar S, Sharma VK, Kaur S (1993) Facial, glossopharyngeal, vagus and hypoglossal nerve palsy in a case of lepromatous leprosy. Indian J Lepr 65:333–336PubMed Dhar S, Sharma VK, Kaur S (1993) Facial, glossopharyngeal, vagus and hypoglossal nerve palsy in a case of lepromatous leprosy. Indian J Lepr 65:333–336PubMed
9.
10.
go back to reference Dinarello CA (1994) The interleukin-1 family: 10 years of discovery. FASEB J 8:1314–1325PubMed Dinarello CA (1994) The interleukin-1 family: 10 years of discovery. FASEB J 8:1314–1325PubMed
11.
go back to reference Dinarello CA (2009) Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol 27:519–550PubMedCrossRef Dinarello CA (2009) Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol 27:519–550PubMedCrossRef
12.
go back to reference Dower SK, Kronheim SR, March CJ, Conlon PJ, Hopp TP, Gillis S, Urdal DL (1985) Detection and characterization of high affinity plasma membrane receptors for human interleukin 1. J Exp Med 162:501–515PubMedCrossRef Dower SK, Kronheim SR, March CJ, Conlon PJ, Hopp TP, Gillis S, Urdal DL (1985) Detection and characterization of high affinity plasma membrane receptors for human interleukin 1. J Exp Med 162:501–515PubMedCrossRef
13.
go back to reference Eiling E, Möller M, Kreiselmaier I, Brasch J, Schwarz T (2007) Schnitzler syndrome treatment failure to rituximab but response to anakinra. J Am Acad Dermatol 57:361–364PubMedCrossRef Eiling E, Möller M, Kreiselmaier I, Brasch J, Schwarz T (2007) Schnitzler syndrome treatment failure to rituximab but response to anakinra. J Am Acad Dermatol 57:361–364PubMedCrossRef
14.
go back to reference Fafutis-Morris M, Guillen-Vargas CM, Navarro-Fierro S, Morales-Ortiz R, Armendariz-Borunda J (1999) Serum IL-1ra is elevated in lepromatous leprosy patients. Int J Lepr Other Mycobact Dis 67:287–291PubMed Fafutis-Morris M, Guillen-Vargas CM, Navarro-Fierro S, Morales-Ortiz R, Armendariz-Borunda J (1999) Serum IL-1ra is elevated in lepromatous leprosy patients. Int J Lepr Other Mycobact Dis 67:287–291PubMed
15.
go back to reference Gubler U, Chua AO, Schoenhaut DS, Dwyer CM, McComas W, Motyka R, Nabavi N, Wolitzky AG, Quinn PM, Familletti PC (1991) Co-expression of two distinct genes is required to generate secreted bioactive cytotoxic lymphocyte maturation factor. Proc Natl Acad Sci USA 88:4143–4147PubMedCrossRef Gubler U, Chua AO, Schoenhaut DS, Dwyer CM, McComas W, Motyka R, Nabavi N, Wolitzky AG, Quinn PM, Familletti PC (1991) Co-expression of two distinct genes is required to generate secreted bioactive cytotoxic lymphocyte maturation factor. Proc Natl Acad Sci USA 88:4143–4147PubMedCrossRef
16.
go back to reference Gupte MD (1999) Vaccine trials in leprosy-Venzuela, Malawi and India. Int J Lepr Other Mycobact Dis 67(4 Suppl):S32–S37PubMed Gupte MD (1999) Vaccine trials in leprosy-Venzuela, Malawi and India. Int J Lepr Other Mycobact Dis 67(4 Suppl):S32–S37PubMed
17.
go back to reference James WD, Berger TG, Elston DM (2006) Hansen’s disease. In: Wolff K, Schachner LA, Hansen RC (eds) Andrews’ clinical dermatology, 10th edn. Saunders Elsevier, Amsterdam, pp 343–352 James WD, Berger TG, Elston DM (2006) Hansen’s disease. In: Wolff K, Schachner LA, Hansen RC (eds) Andrews’ clinical dermatology, 10th edn. Saunders Elsevier, Amsterdam, pp 343–352
18.
go back to reference Juffermans NP, Verbon A, Belisle JT, Hill PJ, Speelman P, van Deventer SJ, van der Poll T (2000) Mycobacterial lipoarabinomannan induces an inflammatory response in the mouse lung. A role for interleukin-1. Am J Respir Crit Care Med 162 (2 pt 1):486–489 Juffermans NP, Verbon A, Belisle JT, Hill PJ, Speelman P, van Deventer SJ, van der Poll T (2000) Mycobacterial lipoarabinomannan induces an inflammatory response in the mouse lung. A role for interleukin-1. Am J Respir Crit Care Med 162 (2 pt 1):486–489
19.
go back to reference Krombach F, Münzing S, Allmeling AM, Gerlach JT, Behr J, Dörger M (1997) Cell size of alveolar macrophages: an interspecies comparison. Environ Health Perspect 105(Suppl 5):1261–1263PubMedCentralPubMedCrossRef Krombach F, Münzing S, Allmeling AM, Gerlach JT, Behr J, Dörger M (1997) Cell size of alveolar macrophages: an interspecies comparison. Environ Health Perspect 105(Suppl 5):1261–1263PubMedCentralPubMedCrossRef
20.
go back to reference Leal AM, Magalhães PK, Souza CS, Foss NT (2006) Pituitary-gonadal hormones and interleukin patterns in leprosy. Trop Med Int Health 11:1416–1421PubMedCrossRef Leal AM, Magalhães PK, Souza CS, Foss NT (2006) Pituitary-gonadal hormones and interleukin patterns in leprosy. Trop Med Int Health 11:1416–1421PubMedCrossRef
21.
go back to reference Lee JH, Chang JH (2003) Changes of plasma interleukin-1 receptor antagonist, interleukin-8 and other serologic markers during chemotherapy in patients with active pulmonary tuberculosis. Korean J Intern Med 18:138–145PubMed Lee JH, Chang JH (2003) Changes of plasma interleukin-1 receptor antagonist, interleukin-8 and other serologic markers during chemotherapy in patients with active pulmonary tuberculosis. Korean J Intern Med 18:138–145PubMed
22.
go back to reference Little D, Khanolkar-Young S, Coulthart A, Suneetha S, Lockwood DN (2001) Immunohistochemical analysis of cellular infiltrate and gamma interferon, interleukin-12, and inducible nitric oxide synthase expression in leprosy type 1 (reversal) reactions before and during prednisolone treatment. Infect Immun 69:3413–3417PubMedCentralPubMedCrossRef Little D, Khanolkar-Young S, Coulthart A, Suneetha S, Lockwood DN (2001) Immunohistochemical analysis of cellular infiltrate and gamma interferon, interleukin-12, and inducible nitric oxide synthase expression in leprosy type 1 (reversal) reactions before and during prednisolone treatment. Infect Immun 69:3413–3417PubMedCentralPubMedCrossRef
23.
go back to reference Martin E, Kamath AT, Briscoe H, Britton WJ (2003) The combination of plasmid interleukin-12 with a single DNA vaccine is more effective than Mycobacterium bovis (Bacille Calmette–Guèrin) in protecting against systemic Mycobacterim avium infection. Immunology 109:308–314PubMedCrossRef Martin E, Kamath AT, Briscoe H, Britton WJ (2003) The combination of plasmid interleukin-12 with a single DNA vaccine is more effective than Mycobacterium bovis (Bacille Calmette–Guèrin) in protecting against systemic Mycobacterim avium infection. Immunology 109:308–314PubMedCrossRef
24.
go back to reference Morgan MM, Clayton CC, Heinricher MM (2004) Dissociation of hyperalgesia from fever following intracerebroventricular administration of interleukin-1beta in the rat. Brain Res 1022:96–100PubMedCrossRef Morgan MM, Clayton CC, Heinricher MM (2004) Dissociation of hyperalgesia from fever following intracerebroventricular administration of interleukin-1beta in the rat. Brain Res 1022:96–100PubMedCrossRef
25.
go back to reference Moubasher AD, Kamel NA, Zedan H, Raheem DD (1998) Cytokines in leprosy, II. Effect of treatment on serum cytokines in leprosy. Int J Dermatol 37:741–746PubMedCrossRef Moubasher AD, Kamel NA, Zedan H, Raheem DD (1998) Cytokines in leprosy, II. Effect of treatment on serum cytokines in leprosy. Int J Dermatol 37:741–746PubMedCrossRef
26.
go back to reference Naafs B (1994) Leprosy reactions: new knowledge. Trop Geogr Med 46:80–84PubMed Naafs B (1994) Leprosy reactions: new knowledge. Trop Geogr Med 46:80–84PubMed
27.
go back to reference Oliveira RB, Ochoa MT, Sieling PA, Rea TH, Rambukkana A, Sarno EN, Modlin RL (2003) Expression of Toll-Like Receptor 2 on human Schwann cells: a mechanism of nerve damage in leprosy. Infect Immun 71:1427–1433PubMedCentralPubMedCrossRef Oliveira RB, Ochoa MT, Sieling PA, Rea TH, Rambukkana A, Sarno EN, Modlin RL (2003) Expression of Toll-Like Receptor 2 on human Schwann cells: a mechanism of nerve damage in leprosy. Infect Immun 71:1427–1433PubMedCentralPubMedCrossRef
28.
go back to reference Oppmann B, Lesley R, Blom B, Timans JC (2000) Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 13:715–725PubMedCrossRef Oppmann B, Lesley R, Blom B, Timans JC (2000) Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 13:715–725PubMedCrossRef
29.
go back to reference Sarno EN, Sampaio EP (1996) The role of inflammatory cytokines in the tissue injury of leprosy. Int J Lepr Other Mycobact Dis 64(4 Suppl): S69–S73 (discussion S73–S74) Sarno EN, Sampaio EP (1996) The role of inflammatory cytokines in the tissue injury of leprosy. Int J Lepr Other Mycobact Dis 64(4 Suppl): S69–S73 (discussion S73–S74)
30.
go back to reference Sasaki S, Takeshita F, Okuda K, Ishii N (2001) Mycobacterium leprae and leprosy: a compendium. Microbial Immunol 45:729–736CrossRef Sasaki S, Takeshita F, Okuda K, Ishii N (2001) Mycobacterium leprae and leprosy: a compendium. Microbial Immunol 45:729–736CrossRef
31.
go back to reference Settas LD, Tsimirikas G, Vosvotekas G, Triantafyllidou E, Nicolaides P (2007) Reactivation of pulmonary tuberculosis in a patient with rheumatoid arthritis during treatment with IL-1 receptor antagonists (anakinra). J Clin Rheumatol 13:219–220PubMedCrossRef Settas LD, Tsimirikas G, Vosvotekas G, Triantafyllidou E, Nicolaides P (2007) Reactivation of pulmonary tuberculosis in a patient with rheumatoid arthritis during treatment with IL-1 receptor antagonists (anakinra). J Clin Rheumatol 13:219–220PubMedCrossRef
32.
go back to reference Sinsimer D, Fallows D, Peixoto B, Krahenbuhl J, Kaplan G, Manca C (2010) Mycobacterium leprae actively modulates the cytokine response in naïve human monocytes. Infect Immun 78:293–300PubMedCentralPubMedCrossRef Sinsimer D, Fallows D, Peixoto B, Krahenbuhl J, Kaplan G, Manca C (2010) Mycobacterium leprae actively modulates the cytokine response in naïve human monocytes. Infect Immun 78:293–300PubMedCentralPubMedCrossRef
33.
go back to reference Triccas JA, Roche PW, Winter N, Feng CG, Butlin CR, Britton WJ (1996) A 35-kilo dalton protein is a major target of the human immune response to Mycobacterium leprae. Infect Immun 64:5171–5177PubMedCentralPubMed Triccas JA, Roche PW, Winter N, Feng CG, Butlin CR, Britton WJ (1996) A 35-kilo dalton protein is a major target of the human immune response to Mycobacterium leprae. Infect Immun 64:5171–5177PubMedCentralPubMed
34.
go back to reference Triccas JA, Winter N, Roche PW, Gilpin A, Kendrick KE, Britton WJ (1998) Molecular and immunological analysis of the Mycobacterium avium homologue of the immuno-dominant Myco-bacterium leprae 35 kDa protein. Infect Immun 66:2684–2690PubMedCentralPubMed Triccas JA, Winter N, Roche PW, Gilpin A, Kendrick KE, Britton WJ (1998) Molecular and immunological analysis of the Mycobacterium avium homologue of the immuno-dominant Myco-bacterium leprae 35 kDa protein. Infect Immun 66:2684–2690PubMedCentralPubMed
35.
go back to reference Van Crevel R, van der Ven-Jongekrijg J, Netea MG, de Lange W, Kullberg BJ, van der Meer JW (1999) Disease-specific ex vivo stimulation of whole blood for cytokine production: applications in the study of tuberculosis. J Immunol Methods 222:145–153PubMedCrossRef Van Crevel R, van der Ven-Jongekrijg J, Netea MG, de Lange W, Kullberg BJ, van der Meer JW (1999) Disease-specific ex vivo stimulation of whole blood for cytokine production: applications in the study of tuberculosis. J Immunol Methods 222:145–153PubMedCrossRef
36.
go back to reference Wang KS, Frank DA, Ritz J (2000) Interleukin-2 enhances the response of natural killer cells to interleukin-12 through up-regulation of the interleukin-12 receptor and STAT4. Blood 95:3183–3190PubMed Wang KS, Frank DA, Ritz J (2000) Interleukin-2 enhances the response of natural killer cells to interleukin-12 through up-regulation of the interleukin-12 receptor and STAT4. Blood 95:3183–3190PubMed
37.
go back to reference WHO (1988) Expert committee on leprosy. WHO 6th report Geneva Technical Report Series, 768, pp 7–50 WHO (1988) Expert committee on leprosy. WHO 6th report Geneva Technical Report Series, 768, pp 7–50
38.
go back to reference Yamamura M, Uyemure K, Deons RJ, Modlin RL (1991) Defining protective responses to pathogens: cytokine profile in leprosy lesions. Science 254:277–279PubMedCrossRef Yamamura M, Uyemure K, Deons RJ, Modlin RL (1991) Defining protective responses to pathogens: cytokine profile in leprosy lesions. Science 254:277–279PubMedCrossRef
Metadata
Title
Assessment of serum level of interleukin-1β and interleukin-12 in leprosy: impact of previous Bacillus Calmitte Guerin vaccination
Authors
Mohammed A. Sallam
Enas A. S. Attia
Marwa S. E. Soliman
Publication date
01-03-2014
Publisher
Springer Berlin Heidelberg
Published in
Archives of Dermatological Research / Issue 2/2014
Print ISSN: 0340-3696
Electronic ISSN: 1432-069X
DOI
https://doi.org/10.1007/s00403-013-1411-0

Other articles of this Issue 2/2014

Archives of Dermatological Research 2/2014 Go to the issue