In vivo and in vitro cytokine profiles and mononuclear cell subsets in sicilian patients with active visceral leishmaniasis

Cillari, Enrìco; Vitale, Giustina; Arcoleo, Francesco; 'Agostino, Pietro D; Mocciaro, C; Gambino, G; Malta, Renato; Stassi, Giorgio; Giordano, Carla; Milano, Salvatore; Mansueto, S

doi:10.1006/cyto.1995.0088

Cited by 63 publications

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“…Kurtzhals et al [27] reported an increase in IFN-g production and lymphoproliferation in response to in vitro stimulation with parasite lipophosphoglycan in Kenyan VL patients. Cillari [28] studied in vivo and in vitro cytokine profiles and mononuclear cell subsets in Sicilian patients with VL at the moment of diagnosis, during treatment and after clinical recovery. The patients showed high concentrations of IL-10 and IFN-g at the beginning of infection; these returned to a normal range following successful chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…The patients showed high concentrations of IL-10 and IFN-g at the beginning of infection; these returned to a normal range following successful chemotherapy. Their studies revealed that the cytokine profile in patients with active VL is not clearly characterized by a Th 2 phenotype as in mice and that both Th 1-like and Th 2-like cells appear to proliferate and be activated [28]. Recently, our group has also determined cytokine mRNA levels in VL patients undergoing monotherapy with IFN-g, sodium antimony gluoconate or amphotericin B lipid complex.…”

Section: Discussionmentioning

confidence: 99%

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Reactive oxygen intermediates, nitrite and IFN-γin Indian visceral leishmaniasis

Kumar

Pai

Sundar

2001

Clinical and Experimental Immunology

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SUMMARY Reactive oxygen intermediates (ROI), nitrite and interferon-gamma (IFN-γ) production were investigated at different times during treatment in 10 patients with visceral leishmaniasis (VL). Hydrogen peroxide (H2O2), superoxide (O2−) and IFN-γ production by cultured monocytes from patients with active VL were significantly lower compared with the healthy controls. In contrast, nitrite levels in the supernatants from monocyte cultures of VL patients were comparable to healthy controls and increased significantly during antileishmanial therapy. On day 20 of treatment, a significant increase in the release of H2O2, O2− and IFN-γ was observed. However, at follow-up, 4 months after the end of treatment, the production of H2O2, O2−, IFN-γ and nitrite had declined significantly. Thus, the impairment in hydrogen peroxide and superoxide production suggests that down-regulation of these mediators may be involved in the reduced killing of parasites by monocytes of active VL patients. Furthermore, the monocytes regained respiratory burst activity as the antileishmanial therapy progressed, suggesting that an immune-based mechanism is involved in successful drug therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Reactive oxygen intermediates, nitrite and IFN-γin Indian visceral leishmaniasis

Kumar

Pai

Sundar

2001

Clinical and Experimental Immunology

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“…Although some studies evaluating cytokines in serum samples have either not detected or found low concentrations of 69,70 , other studies have produced conflicting results. IFN-g was detected in 17 of 44 patients in Iran 2 and in 13 of 15 patients in Brazil 20 ; in addition, high levels have been confirmed in patients in Asia, Europe, Africa, and Brazil 9,15,31,32,50,52 . These differing results are most likely not related to the selected patient groups or to the Leishmania species involved, but rather to the samples that were analyzed.…”

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confidence: 86%

“…Some studies show that the lymphoproliferative response to mitogens is also affected 14,29,34 but it is primarily the Leishmania antigen-driven response that is disturbed. In addition, IL-12 is absent in Leishmania antigen-induced cytokine production in PBMC culture supernatants 28 , and IL-2 and IFN-g are either absent or present in low levels 12,15,28,39 . These findings reinforce the view that it is mainly the Th1 response that is suppressed.…”

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confidence: 99%

“…It has also been found to be important in susceptibility to visceral leishmaniasis 30,49 . It has been detected in different samples of human visceral leishmaniasis: as mRNA in bone marrow 36 , lymph node 27 , and spleen 38 aspirates and at high levels in serum 1,2,15,40,50,52,63,69 ; for further information see 51 . As mentioned earlier, the possible effect of IL-10 on the production of, or proliferation of IFN-g producing cells 11,28 may not be important given the high activation of the immune response in lymphoid organs during active disease.…”

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Immunoactivation and immunopathogeny during active visceral leishmaniasis

Goto

Prianti

2009

Rev. Inst. Med. trop. S. Paulo

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SUMMARYVisceral leishmaniasis is caused by protozoan parasites of the Leishmania donovani complex. During active disease in humans, high levels of IFN-g and TNF-a detected in blood serum, and high expression of IFN-g mRNA in samples of the lymphoid organs suggest that the immune system is highly activated. However, studies using peripheral blood mononuclear cells have found immunosuppression specific to Leishmania antigens; this poor immune response probably results from Leishmania antigen-engaged lymphocytes being trapped in the lymphoid organs. To allow the parasites to multiply, deactivating cytokines IL-10 and TGF-b may be acting on macrophages as well as anti-Leishmania antibodies that opsonize amastigotes and induce IL-10 production in macrophages. These high activation and deactivation processes are likely to occur mainly in the spleen and liver and can be confirmed through the examination of organ samples. However, an analysis of sequential data from studies of visceral leishmaniasis in hamsters suggests that factors outside of the immune system are responsible for the early inactivation of inducible nitric oxide synthase, which occurs before the expression of deactivating cytokines. In active visceral leishmaniasis, the immune system actively participates in non-lymphoid organ lesioning. While current views only consider immunocomplex deposition, macrophages, T cells, cytokines, and immunoglobulins by diverse mechanism also play important roles in the pathogenesis. KEYWORDS:Visceral leishmaniasis; Human; Immunosuppression; Immunoactivation; Cytokines; Immunopathogenesis.Visceral leishmaniasis is caused by protozoa of the genus Leishmania that are transmitted to mammalian hosts, including humans, by phlebotomine sandflies. The disease is present in 66 countries in tropical and subtropical regions, and 90% of cases occur in India, Sudan, Bangladesh, Nepal, and Brazil. It is estimated that there are 500,000 new cases a year worldwide 68 , and 3,000 new cases occur each year in Brazil 48 . Until recently, the disease was thought to be caused by three species of the Leishmania donovani complex: Leishmania (Leishmania) donovani, L. (L.) infantum, and Leishmania (L.) chagasi (a species present in Brazil). There is now debate, however, over whether L. (L). infantum and Leishmania (L.) chagasi are the same 44 or different 60 species. In this review, the names of the three species will be used as in the original publications. Leishmania (Leishmania) donovani is present in East Africa, India, and parts of the Middle East, while L. (L.) infantum in Europe, North Africa, and South and Central America. Human infections can be asymptomatic or can manifest as oligosymptomatic and progressive diseases; progressive cases can involve hepatosplenomegaly, fever, pancytopenia, hypergammaglobulinemia, and serious weight loss 4 . During active visceral leishmaniasis, the parasite multiplies within the cells of the mononuclear phagocyte system in the spleen, liver, and bone marrow, and the disease is fatal if untreated.Studies...

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Detection of CD4+CD45RO+T Lymphocytes Producing IL-4 in Response to Antigens onPlasmodium falciparumErythrocytes: Anin VitroCorrelate of Protective Immunity Induced with AttenuatedPlasmodium falciparumSporozoites

Bergmann

Ballou

Krzych

1997

Cellular Immunology

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In vivo and in vitro cytokine profiles and mononuclear cell subsets in sicilian patients with active visceral leishmaniasis

Cited by 63 publications

References 0 publications

Reactive oxygen intermediates, nitrite and IFN-γin Indian visceral leishmaniasis

Reactive oxygen intermediates, nitrite and IFN-γin Indian visceral leishmaniasis

Immunoactivation and immunopathogeny during active visceral leishmaniasis

Detection of CD4+CD45RO+T Lymphocytes Producing IL-4 in Response to Antigens onPlasmodium falciparumErythrocytes: Anin VitroCorrelate of Protective Immunity Induced with AttenuatedPlasmodium falciparumSporozoites

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