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.
D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D001706:Biopsy; D002648:Child; D015331:Cohort Studies; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D005260:Female; D015964:Gene Expression Regulation, Bacterial / Q000276:immunology*; D006801:Humans; D007918:Leprosy / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D008297:Male; D008911:Minocycline / Q000627:therapeutic use; D009166:Mycobacterium leprae / Q000235:genetics* / Q000276:immunology; D015242:Ofloxacin / Q000627:therapeutic use; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012293:Rifampin / Q000627:therapeutic use; D018417:Th1 Cells / Q000276:immunology
D000907:Antibodies, Bacterial; D016207:Cytokines; D012333:RNA, Messenger; D012367:RNA, Viral; D015242:Ofloxacin; D008911:Minocycline; D012293:Rifampin