In situ type 1 cytokine gene expression and mechanisms associated with early leprosy progression.

We explored the prognostic value of in situ cytokine patterns in 39 patients with single-skin-lesion paucibacillary leprosy before single-dose therapy, with 3 years of follow-up. Interferon (IFN)-gamma, interleukin (IL)-12, IL-10, IL-4, tumor necrosis factor (TNF)-alpha, and macrophage inflammatory protein (MIP)-1alpha mRNA was quantified in skin biopsy samples at diagnosis, and Mycobacterium leprae DNA was detected in 51.4% of cases. Type 1 immunity predominance with measurable IFN-gamma and undetectable IL-4, which is indicative of effective cell-mediated immunity, is compatible with both the reversal reactions (33.3%) and the resolution of lesions (64.1%) observed. A positive correlation between IL-12 and IFN-gamma indicated type 1 polarization via IL-12. The TNF-alpha/MIP-1alpha correlation implied the TNF-alpha induction of chemokines, which is important for granuloma formation. Positive correlations between key regulatory cytokines-IL-10 and IFN-gamma, IL-10 and IL-12, and IL-10 and TNF-alpha-suggests that there may be some level of an intralesional pro- or anti-inflammatory mechanism essential in avoiding immunopathology.

[1]  I. Orme,et al.  Materials and Methods Briefdefinitive Report Disseminated Tuberculosis in Interferon 7 Gene-disrupted Mice , 2022 .

[2]  Andrew G. D. Bean,et al.  TNF Regulates Chemokine Induction Essential for Cell Recruitment, Granuloma Formation, and Clearance of Mycobacterial Infection1 , 2002, The Journal of Immunology.

[3]  I. Orme,et al.  The study of Mycobacterium leprae infection in interferon-gamma gene--disrupted mice as a model to explore the immunopathologic spectrum of leprosy. , 2002, The Journal of infectious diseases.

[4]  J. Casanova,et al.  Heterogeneity in the granulomatous response to mycobacterial infection in patients with defined genetic mutations in the interleukin 12‐dependent interferon‐gamma production pathway , 2002, International journal of experimental pathology.

[5]  D. Scollard,et al.  Distinct histopathological patterns in single lesion leprosy patients treated with single dose therapy (ROM) in the Brazilian Multicentric Study. , 2001, International journal of leprosy and other mycobacterial diseases : official organ of the International Leprosy Association.

[6]  K. Shuai,et al.  A Role for IL-12 Receptor Expression and Signal Transduction in Host Defense in Leprosy1 , 2001, The Journal of Immunology.

[7]  S. Chensue,et al.  Chemokine expression dynamics in mycobacterial (type-1) and schistosomal (type-2) antigen-elicited pulmonary granuloma formation. , 2001, The American journal of pathology.

[8]  B. Spellberg,et al.  Type 1/Type 2 immunity in infectious diseases. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[9]  R. Döffinger,et al.  Human interferon‐g‐mediated immunity is a genetically controlled continuous trait that determines the outcome of mycobacterial invasion , 2000, Immunological reviews.

[10]  A. Andrade,et al.  Single lesion paucibacillary leprosy: baseline profile of the Brazilian Multicenter Cohort Study. , 2000, International journal of leprosy and other mycobacterial diseases : official organ of the International Leprosy Association.

[11]  Saraiva,et al.  Cytokine mRNA Expression in Leprosy: a Possible Role for Interferon‐γ and Interleukin‐12 in Reactions (RR and ENL) , 1999, Scandinavian journal of immunology.

[12]  J. Casanova,et al.  Novel human immunodeficiencies reveal the essential role of type-I cytokines in immunity to intracellular bacteria. , 1998, Immunology today.

[13]  A. L. de Andrade,et al.  Assessment of anti-PGL-I as a prognostic marker of leprosy reaction. , 1998, International journal of leprosy and other mycobacterial diseases : official organ of the International Leprosy Association.

[14]  W. Britton.  The management of leprosy reversal reactions. , 1998, Leprosy review.

[15]  R. Singh,et al.  The possible role of interleukin (IL)-12 and interferon-gamma-inducing factor/IL-18 in protection against experimental Mycobacterium leprae infection in mice. , 1998, Clinical immunology and immunopathology.

[16]  G. Trinchieri,et al.  The role of IL‐12 in the maintenance of an established Th1 immune response in experimental leishmaniasis , 1998, European journal of immunology.

[17]  D. Williams,et al.  Polymerase chain reaction assay for the detection and identification of Mycobacterium leprae in patients in the United States. , 1998, American journal of clinical pathology.

[18]  P. Klatser,et al.  DNA amplification for detection of leprosy and assessment of efficacy of leprosy chemotherapy. , 1998, International journal of leprosy and other mycobacterial diseases : official organ of the International Leprosy Association.

[19]  T. Gillis,et al.  Global elimination of leprosy , 1998 .

[20]  C. K. Job,et al.  Role of polymerase chain reaction in the diagnosis of early leprosy. , 1997, International journal of leprosy and other mycobacterial diseases : official organ of the International Leprosy Association.

[21]  P. Das,et al.  Reversal reaction in borderline leprosy is associated with a polarized shift to type 1-like Mycobacterium leprae T cell reactivity in lesional skin: a follow-up study. , 1997, Journal of immunology.

[22]  A. Sher,et al.  Defects in cell-mediated immunity affect chronic, but not innate, resistance of mice to Mycobacterium avium infection. , 1997, Journal of immunology.

[23]  U. Boehm,et al.  Cellular responses to interferon-gamma. , 1997, Annual review of immunology.

[24]  D. Lockwood,et al.  Tumour necrosis factor‐alpha (TNF‐α) synthesis is associated with the skin and peripheral nerve pathology of leprosy reversal reactions , 1995, Clinical and experimental immunology.

[25]  J. Flynn,et al.  An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection , 1993, The Journal of experimental medicine.

[26]  I. Orme,et al.  Disseminated tuberculosis in interferon gamma gene-disrupted mice , 1993, The Journal of experimental medicine.

[27]  B. Bloom,et al.  Cytokine patterns of immunologically mediated tissue damage. , 1992, Journal of immunology.

[28]  K. Weinberg,et al.  Defining protective responses to pathogens: cytokine profiles in leprosy lesions. , 1991, Science.

[29]  J. Convit,et al.  Differing lymphokine profiles of functional subsets of human CD4 and CD8 T cell clones. , 1991, Science.

[30]  M. Piccinni,et al.  Allergen- and bacterial antigen-specific T-cell clones established from atopic donors show a different profile of cytokine production. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[31]  R. Booth,et al.  The use of a specific DNA probe and polymerase chain reaction for the detection of Mycobacterium leprae. , 1990, The Journal of infectious diseases.

[32]  R. Coffman,et al.  Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. , 1986, Journal of immunology.

[33]  Ridley Ds,et al.  Classification of leprosy according to immunity. A five-group system. , 1966 .

[34]  D. Ridley,et al.  Classification of leprosy according to immunity. A five-group system. , 1966, International journal of leprosy and other mycobacterial diseases : official organ of the International Leprosy Association.