02282nas a2200445 4500000000100000008004100001260001600042653001500058653001000073653002600083653001100109653001000120653001900130653001400149653001100163653004200174653001100216653001200227653000900239653001600248653002500264653001400289653001400303653005200317653001300369653001900382653001500401653001400416100001400430700001500444700001300459700001800472700003500490245010200525300001200627490000800639050001700647520115800664022001401822 2003 d c2003 Oct 0110aAdolescent10aAdult10aAntibodies, Bacterial10aBiopsy10aChild10aCohort Studies10aCytokines10aFemale10aGene Expression Regulation, Bacterial10aHumans10aleprosy10aMale10aMinocycline10aMycobacterium leprae10aOfloxacin10aPrognosis10aReverse Transcriptase Polymerase Chain Reaction10aRifampin10aRNA, Messenger10aRNA, Viral10aTh1 Cells1 aStefani M1 aMartelli C1 aGillis T1 aKrahenbuhl JL1 aBrazilian Leprosy Study Group 00aIn situ type 1 cytokine gene expression and mechanisms associated with early leprosy progression. a1024-310 v188 aSTEFANI 20033 a

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.

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