Clinical and immunological features of patients with atopy and concomitant HTLV-1 infection

Human T-cell lymphotropic virus type 1 (HTLV-1) induces an exacerbated type 1 immune response characterized by high spontaneous IFN-γ and TNF-α production. Allergic rhinitis and asthma are associated with the type 2 immune response, with elevated secretion of IL-4 and IL-5. The aim of this study was to characterize the immune response in atopic HTLV-1 carriers. The cytokine profile of atopic HTLV-1 carriers (N = 10; all females) was compared with that of non-atopic HTLV-1 carriers (N = 14; 9 females and 5 males). Mean patient age of atopic and non-atopic groups was 45 ± 8 and 38 ± 11 years, respectively. All atopic HTLV-1 carriers had rhinitis with or without asthma and a skin prick test positive for Dermatophagoides pteronyssinus antigen 1 (Derp-1). There was no difference in cytokine levels between the two groups in unstimulated peripheral blood mononuclear cell cultures. In cultures stimulated with Derp-1, IFN-γ levels tended to be higher (P = 0.06) and IL-5 levels were higher (P = 0.02) in atopic HTLV-1 patients than in non-atopic subjects. In contrast, IL-10 was lower (P = 0.004) in atopic than in non-atopic HTLV-1-infected subjects. This study shows that HTLV-1 infection with an exaggerated type 1 immune response does not prevent atopy. In this case, the exacerbated type 1 and type 2 immune responses were due to a lack of IL-10 production, a cytokine that plays an important role in down-modulating type 1 and type 2 immune responses and in preventing the development of chronic inflammatory diseases.

Tratamento da leishmaniose mucosa com sulfato de aminosidine: resultados de dois anos de acompanhamento / Treatment of mucosal leishmaniasis with aminosidine sulfate: results of two year follow-up

In 1996, 20 of 21 patients with mucosal leishmaniasis, treated in 1994 with aminosidine sulfate, 16mg/kg/day salt, by intramuscular injection for 20 days, were clinically evaluated. One patient died due to disease not related to mucosal leishmaniasis. Seven of 14 patients (66.7% N = 21) who achieved complete remission three months after treatment remained clinically cured 24 months later and seven relapsed in the same period (50% N = 14). Sorological follow-up showed poor correlation with the results of clinical examination.

Em 1996 foram avaliados clinicamente 20 dos 21 pacientes com leishmaniose mucosa, tratados em 1994 com sulfato de aminosidine 16mg do sal/kg/dia, intramuscular, por 20 dias. Um paciente foi a óbito por causas não relacionadas com a leishmaniose mucosa. Dos 14 pacientes (66,7% N = 21) que inicialmente alcançaram a remissão completa dos sinais e sintomas durante os três primeiros meses de seguimento, sete (50% N = 14) permaneceram livres de doença por 24 meses e sete pacientes apresentaram recidiva neste período. O acompanhamento sorológico mostrou pobre correlação com a avaliação clínica.

Cytokine profile and pathology in human leishmaniasis

The clinical spectrum of leishmaniasis and control of the infection are influenced by the parasite-host relationship. The role of cellular immune responses of the Th1 type in the protection against disease in experimental and human leishmaniasis is well established. In humans, production of IFN-gamma is associated with the control of infection in children infected by Leishmania chagasi. In visceral leishmaniasis, an impairment in IFN-gamma production and high IL-4 and IL-10 levels (Th2 cytokines) are observed in antigen-stimulated peripheral blood mononuclear cells (PBMC). Moreover, IL-12 restores IFN-gamma production and enhances the cytotoxic response. IL-10 is the cytokine involved in down-regulation of IFN-gamma production, since anti-IL-10 monoclonal antibody (mAb) restores in vitro IFN-gamma production and lymphoproliferative responses, and IL-10 abrogates the effect of IL-12. In cutaneous and mucosal leishmaniasis, high levels of IFN-gamma are found in L. amazonensis-stimulated PBMC. However, low or absent IFN-gamma levels were observed in antigen-stimulated PBMC from 50 percent of subjects with less than 60 days of disease (24 + 26 pg/ml). This response was restored by IL-12 (308 + 342 pg/ml) and anti-IL-10 mAb (380 + 245 pg/ml) (P<0.05). Later during the disease, high levels of IFN-gamma and TNF-alpha are produced both in cutaneous and mucosal leishmaniasis. After treatment there is a decrease in TNF-alpha levels (366 + 224 pg/ml before treatment vs 142 + 107 pg/ml after treatment, P = 0.02). Although production of IFN-gamma and TNF-alpha might be involved in the control of parasite multiplication in the early phases of Leishmania infection, these cytokines might also be involved in the tissue damage seen in tegumentary leishmaniasis.