title: Balance of IL-10 and interferon-gamma plasma levels in human visceral leishmaniasis: implications in the pathogenesis.
abstract: BACKGROUND
  Leishmaniasis remains a serious public health problem in several parts of the developing world. Effective prophylactic measurements are hampered by imprecise comprehension of different aspects of the disease, including its immunoregulation. A better comprehension of immunoregulation in human VL may be useful both for designing and evaluating immunoprophylaxis.
  
  
  METHODS
  To explore immunoregulatory mechanisms, 20 visceral leishmaniasis (VL) patients were evaluated during active disease and at different periods up to one year after treatment determining their plasma cytokine levels, clinical parameters (palpable spleen and liver) and antibody levels.
  
  
  RESULTS
  Elevated plasma levels of IFN-gamma and of IL-12 p40 were observed during active disease, significantly decreasing after treatment whereas in vitro Leishmania antigen-stimulated IFN-gamma production by PBMC exhibited an inverse pattern being low during disease and increasing steadily thereafter. Absence of IFN-gamma activity is a hallmark of VL. The main candidate for blunting IFN-gamma activity is IL-10, a cytokine highly elevated in plasma with sharp decrease after treatment. Activity of IL-10 is inferred by high levels of anti-Leishmania specific IgG1 and IgG3. TGF-beta had elevated total, but not of active, levels lessening the likelihood of being the IFN-gamma counterpart. Spleen or liver size presented a steady decrease but return to normal values at only 120 days after treatment. Anti-Leishmania IgG (total and subclasses) levels and DTH or Leishmania-stimulated lymphocyte proliferation conversion to positive also present a slow decrease after treatment. IL-6 plasma levels were elevated in only a few patients.
  
  
  CONCLUSIONS
  Taken together our results suggest that IFN-gamma and IL-10 are the molecules most likely involved in determining fate of disease. After treatment, there is a long delay before the immune profile returns to normal what precludes using plasma cytokine levels as criteria of cure as simpler clinical evaluations, as a palpable spleen or liver, can be used.
authors.affiliation: Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz-FIOCRUZ, Salvador, BA, Brazil. acaldas@elo.com.br
authors.forename: Arlene
authors.initials: A
authors.lastname: Caldas
authors.forename: Cecília
authors.initials: C
authors.lastname: Favali
authors.forename: Dorlene
authors.initials: D
authors.lastname: Aquino
authors.forename: Vera
authors.initials: V
authors.lastname: Vinhas
authors.forename: Johan
authors.initials: J
authors.lastname: van Weyenbergh
authors.forename: Cláudia
authors.initials: C
authors.lastname: Brodskyn
authors.forename: Jackson
authors.initials: J
authors.lastname: Costa
authors.forename: Manoel
authors.initials: M
authors.lastname: Barral-Netto
authors.forename: Aldina
authors.initials: A
authors.lastname: Barral
mesh_terms: D000293:Adolescent; D000328:Adult; D000981:Antiprotozoal Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D007371:Interferon-gamma / Q000097:blood* / Q000276:immunology; D016753:Interleukin-10 / Q000097:blood* / Q000276:immunology; D007898:Leishmaniasis, Visceral / Q000097:blood* / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D008099:Liver / Q000473:pathology; D008297:Male; D008536:Meglumine / Q000627:therapeutic use; D000077485:Meglumine Antimoniate; D008875:Middle Aged; D009929:Organ Size; D009942:Organometallic Compounds / Q000627:therapeutic use; D011446:Prospective Studies; D013154:Spleen / Q000473:pathology; D013997:Time Factors
chemical_list: D000981:Antiprotozoal Agents; D007074:Immunoglobulin G; D009942:Organometallic Compounds; D016753:Interleukin-10; D008536:Meglumine; D000077485:Meglumine Antimoniate; D007371:Interferon-gamma