Balance of IL-10 and Interferon-γ plasma levels in human visceral leishmaniasis: Implications in the pathogenesis

Arlene Caldas¹^,2 , Cecília Favali¹ , Dorlene Aquino¹^,2 , Vera Vinhas¹ , Johan van Weyenbergh¹^,4 , Cláudia Brodskyn¹^,4 , Jackson Costa¹ , Manoel Barral-Netto¹^,3^,4 and Aldina Barral¹^,3^,4

¹Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz – FIOCRUZ, Salvador, BA, Brazil

²Department of Nursing, Federal University of Maranhão, UFMA, São Luís, MA, Brazil

³Faculdade de Medicina da Bahia. Universidade Federal da Bahia, UFBA, Salvador, BA, Brazil

⁴Institute of Investigation in Immunology, Salvador, Bahia, Brazil

author email corresponding author email

BMC Infectious Diseases 2005, 5:113doi:10.1186/1471-2334-5-113


Published:	19 December 2005

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-γ and of IL-12 p40 were observed during active disease, significantly decreasing after treatment whereas in vitro Leishmania antigen-stimulated IFN-γ production by PBMC exhibited an inverse pattern being low during disease and increasing steadily thereafter. Absence of IFN-γ activity is a hallmark of VL. The main candidate for blunting IFN-γ 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-β had elevated total, but not of active, levels lessening the likelihood of being the IFN-γ 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.

Conclusion

Taken together our results suggest that IFN-γ 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.