ABSTRACT
Lung disease during active human visceral leishmaniasis is frequently reported. As such, studies have associated pulmonary symptoms to interstitial pneumonitis with a mononuclear infiltrate. However, the immune response in this condition has never been described before. The aim of this study was to determine the immunophenotypic pattern and cytokine profile of lung involvement (IPL) in human visceral leishmaniasis. Quantitative methods of analysis were performed using immunohistochemistry, and were compared with a control group of normal lung. Interstitial macrophages and cd8 cells were increased in IPL, and IL-4 as well as TNF-alpha displayed increased expression when compared to the control group. This inflammatory process with a Th2 pattern, as suggested by increased IL-4 and low IFN-gamma expression, is consistent with the immune response in other organs of visceral leishmaniasis. The microenvironment of the immune response in this condition is associated with lung disease in patients with interstitial pneumonitis related to visceral leishmaniasis, increasing the chance of bacterial infection.
Subject(s)
Leishmaniasis, Visceral/immunology , Lung Diseases, Interstitial/immunology , Lung Diseases, Parasitic/immunology , CD8-Positive T-Lymphocytes/immunology , Cell Proliferation , Humans , Immunohistochemistry , Interferon-gamma/biosynthesis , Interleukin-4/biosynthesis , Leishmaniasis, Visceral/complications , Lung Diseases, Interstitial/parasitology , Lung Diseases, Parasitic/etiology , Macrophages/immunology , Tumor Necrosis Factor-alpha/biosynthesisABSTRACT
We can consider the Leishmania major-infected hamster as an interesting model of visceral leishmaniasis. Every hamster infected with L. major strain 70 by peritoneal route developed visceral dissemination of the parasite. When immunological parameters were considered, we saw data quite similar to those presented by visceral leishmaniasis patients: negative leishmanin skin test and presence of anti-leishmania antibody. Histopathological analysis showed dissemination of the parasite mainly to liver and spleen. The former organ showed hypertrophy and hyperplasia of Kupffer cells with focal areas of inflammatory infiltration in nodular pattern. The spleen disclosed intense proliferation and enlargement of mononuclear phagocytic cells, sometimes revealing nodular configuration. Anti-leishmania antibodies were easily detected by indirect immunofluorescent technique in this model. Immunomodulation by Cyclophosphamide decreased the anti-leishmania antibody and delayed-type hypersensitivity test results suggested that hamster was able to develop reaction to leishmania antigen, although leishmanin skin test was negative in the L. major-infected animals. We consider the L. major-infected hamster a useful model for visceral leishmaniasis study because of the similarity of immunological reactions to parasite antigen in human disease.