ESTIMULAÇÃO COMBINADA DE IL-12 E IL-15 PROMOVE A RESPOSTA IMUNE CELULAR EM CÃES COM LEISHMANIOSE VIA IFN-y

A Leishmaniose Visceral (LV) é causada nas Américas, pelo protozoário intracelular obrigatório Leishmania infantum e os cães domésticos são os principais reservatórios urbanos do parasita e em áreas endêmicas, o aumento da LV em humanos tem sido associado ao aumento da infecção canina. Os atuais medicamentos disponíveis para a Leishmaniose Canina (CanL) não são completamente eficientes e meses após o tratamento a maioria dos cães apresentam recidiva, indicando a necessidade de buscar formas alternativas de tratamento. Na CanL, cães desenvolvem uma resposta imune celular (Th1) ineficiente para combater o parasita e a estimulação das vias de citocinas em células de defesa com proteínas recombinantes, tem o potencial de se tornar parte de métodos imunoterapêuticos eficazes. Neste estudo, as citocinas recombinantes caninas (IL-12, IL-2, IL-15 e IL-7) e o receptor solúvel de IL-10R1 (sIL-10R1), com atividade antagonista, foram avaliadas pela primeira vez em combinações (IL-12/IL- 2, IL-12/IL-15, IL-12/sIL-10R1, IL-15/IL-7) ou isoladamente (sIL-10R1) quanto à capacidade imunomodulatória em células mononucleares do sangue periférico (sigla em inglês PBMC) de cães com leishmaniose. Todas as combinações de proteínas recombinantes testadas mostraram melhorar a resposta linfoproliferativa. Além disso, as combinações de IL-12/IL-2 e IL-12/IL-15 promoveram a diminuição na expressão da proteína Programed Cell Death 1 (PD-1) nos linfócitos. Estas mesmas combinações de citocinas e IL-12/sIL-10R1 induziram a produção de IFN-y nas PBMCs. Além disso, a combinação de IL-12/IL-15 aumentou expressão de Tbet nos linfócitos. Esses achados estimulam o uso de IL-12 e IL-15 em futuros estudos in vivo com o objetivo de obter a polarização da resposta imune celular em cães com leishmaniose, o que pode contribuir para o desenvolvimento de um tratamento efetivo contra a CanL.

Visceral Leishmaniasis (LV) is caused in the Americas by the obligate intracellular protozoan Leishmania infantum and domestic dogs are the major urban reservoirs of the parasite and in endemic areas, and increase LV in humans has been associated with increased canine infection. The current medications available for Canine Leishmaniasis (CanL) are not completely effective and months after treatment most dogs present with relapse, indicating the necessity to looking for alternative forms of treatment. In CanL, dogs develop an ineffective cellular immune response (Th1) to combat the parasite. Then, the stimulation of cytokine pathways in defense cells with recombinant proteins, has the potential to become part of effective immunotherapeutic methods. In this study, the canine recombinant cytokines (IL-12, IL-2, IL-15 and IL-7) and the soluble receptor of IL-10R1 (sIL-10R1) with antagonistic activity, were evaluated for the first time in combinations IL-12/IL-2, IL-12/IL-15, IL- 12/sIL-10R1, IL-15/IL-7) or alone (sIL-10R1) for their immunomodulatory capacity in peripheral blood mononuclear cells (PBMC) from dogs with leishmaniasis. All combinations of recombinant proteins tested were shown to improve lymphoproliferative response. Further, combinations of IL-12/IL-2 and IL-12/IL-15 promoted decrease in programmed cell death protein 1 (PD-1) expression in lymphocytes. These same combinations of cytokines and IL-12/casIL-10R1 induced IFN-y production in PBMC. Furthermore, the combination of IL-12/IL-15 led to an increased T-bet expression . These findings encourage the use of IL-12 and IL-15 in future in vivo studies aiming to get polarization of cellular immune response in dogs with leishmaniasis, that may contribute to development of an effective treatment against CanL.

Correlation between serum levels of interleukins 10 and 12 and thrombocytopenia in hepatitis C cirrhotic (class A) patients

Hepatitis C virus (HCV) patients commonly have low platelet counts; however, the exact role of HCV infection in thrombocytopenia is unknown. This work aimed to study the serum levels of interleukins (IL) 10 and 12 in patients with mild and moderate thrombocytopenia associated with chronic hepatitis C infection. Our study included 15 patients with chronic HCV infection and newly diagnosed isolated autoimmune thrombocytopenia (Group I) and 15 patients with chronic HCV infection and normal platelet count as controls (Group II). All patients were examined for personal history and clinical aspects, complete blood count, bone marrow aspiration, liver function tests, HCV antibody assay by ELISA and polymerase chain reaction (PCR), abdominal ultrasound, Helicobacter pylori stool antigen test, evaluation of serum levels of IL-10, IL-12 and platelet specific antibodies. Our results revealed that eight patients from Group l had mild thrombocytopenia and seven patients had moderate thrombocytopenia. Serum IL-10 level was significantly elevated (t = 9.301, p < 0.001) while serum IL-12 showed a significant decrease (t = 6.502, p < 0.001) in Group I compared to the control group. No correlation was detected between platelet counts and the serum levels of either IL-10 [r = 0.454, p = 0.089 (Group I), r = 0.038, p = 0.89 (Group II)] or IL-12 [r = 0.497, p = 0.06 (Group I), r = 0.499, p = 0.058 (Group II)]. However, in Group I, a significant correlation was present only between moderate thrombocytopenia and serum levels of either IL-10 (r = 0.794, p = 0.033) or IL-12 (r = 0.967, p = 0.001), while no correlation was detected between these interleukin parameters and mild thrombocytopenia (r = 0.311 and p = 0.453 for IL-10 and r = -0.08 and p = 0.851 for IL-12). Based on our data, we may conclude that interleukins 10 and 12 are involved in low platelet levels.(AU)

Correlation between serum levels of interleukins 10 and 12 and thrombocytopenia in hepatitis C cirrhotic (class A) patients

Hepatitis C virus (HCV) patients commonly have low platelet counts; however, the exact role of HCV infection in thrombocytopenia is unknown. This work aimed to study the serum levels of interleukins (IL) 10 and 12 in patients with mild and moderate thrombocytopenia associated with chronic hepatitis C infection. Our study included 15 patients with chronic HCV infection and newly diagnosed isolated autoimmune thrombocytopenia (Group I) and 15 patients with chronic HCV infection and normal platelet count as controls (Group II). All patients were examined for personal history and clinical aspects, complete blood count, bone marrow aspiration, liver function tests, HCV antibody assay by ELISA and polymerase chain reaction (PCR), abdominal ultrasound, Helicobacter pylori stool antigen test, evaluation of serum levels of IL-10, IL-12 and platelet specific antibodies. Our results revealed that eight patients from Group l had mild thrombocytopenia and seven patients had moderate thrombocytopenia. Serum IL-10 level was significantly elevated (t = 9.301, p < 0.001) while serum IL-12 showed a significant decrease (t = 6.502, p < 0.001) in Group I compared to the control group. No correlation was detected between platelet counts and the serum levels of either IL-10 [r = 0.454, p = 0.089 (Group I), r = 0.038, p = 0.89 (Group II)] or IL-12 [r = 0.497, p = 0.06 (Group I), r = 0.499, p = 0.058 (Group II)]. However, in Group I, a significant correlation was present only between moderate thrombocytopenia and serum levels of either IL-10 (r = 0.794, p = 0.033) or IL-12 (r = 0.967, p = 0.001), while no correlation was detected between these interleukin parameters and mild thrombocytopenia (r = 0.311 and p = 0.453 for IL-10 and r = –0.08 and p = 0.851 for IL-12). Based on our data, we may conclude that interleukins 10 and 12 are involved in low platelet levels.(AU)