ABSTRACT
Chronic mucocutaneous candidiasis (CMC) is a rare syndrome characterized by persistent and refractory infections of the skin, nails and mucosal tissues by yeasts of the genus Candida. Defects in the cellular limb of the immune system are well documented in CMC patients, but non-specific immune defects, such as myeloperoxidase deficiency or phagocyte chemotaxis disorders, have also been described. Nonetheless, the underlying defect(s) remains poorly understood, and further studies are required. We studied eight CMC patients without endocrinopathies, who showed (i) low normal proliferative response to phytohaemagglutinin (PHA), (ii) partially defective response to pokeweed mitogen (PWM), and (iii) impaired response to Candida and PPD antigens. Furthermore, peripheral blood mononuclear cells (PBMC) from CMC patients produced lower levels of type-1 cytokines (IL-2 and interferon-gamma) in response to Candida antigens, compared with control individuals. Conversely, we did not observe an enhancement of IL-4 and IL-10 in the patients, suggesting that, even though Th1 cytokines are decreased, the Th2 response is not increased in CMC. Nevertheless, the synthesis of these cytokines was normal when induced by PHA. We also observed an increased antigen-induced apoptosis in lymphocytes from the patients compared with controls, and this applied both to Candida and PPD antigens. Lastly, innate immunity defects were investigated. We observed an impairment of natural killer activity against K-562 target cells in half of the studied patients. These findings corroborate the extensive clinical and laboratory variability of CMC, which requires further studies on a larger number of patients to be better understood.
Subject(s)
Candidiasis, Chronic Mucocutaneous/immunology , Immunity, Cellular , Adolescent , Adult , Cells, Cultured , Child , Child, Preschool , Female , Humans , Lymphocyte Activation , Male , T-Lymphocytes, Cytotoxic/immunologyABSTRACT
O efeito imunomodulatorio da Cimetidine (CIM), um antagonista do receptor de histamina-tipo 2, foi avaliado na resposta blastogenica a Con A em celulas de ratos Wistar Furth (WF) infectados pela cepa Y de Trypanosoma cruzi (T.cruzi). Foi observado que apenas na concentracao de "10 POT. -3"M de Cimetidine houve amplificacao da resposta blastogenica de esplenocitos normais a Con A. Entretanto, a capacidade mitogenica de esplenocitos de animais infectados foi restaurada na presenca de molaridades da droga que variaram entre "10 POT. -8" a "10 POT. -3". Os resultados demonstraram que a CIM tem o potencial de modular a resposta mitogenica de celulas de animais infectados pelo T.cruzi, sugerindo um papel imunoregulatorio da histamina e/ou celulas que expressam receptores H2 nesta infeccao.
Subject(s)
Rats , Male , Female , Animals , Adjuvants, Immunologic/pharmacology , Chagas Disease/immunology , Cimetidine/pharmacology , Spleen/cytology , Concanavalin A/pharmacology , Rats, Inbred WF , Receptors, Histamine H2/drug effects , Receptors, Histamine H2/immunology , Spleen/drug effects , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/immunologyABSTRACT
The immunomodulatory effect of cimetidine (CIM), a histamine type-2 receptor antagonist, was evaluated in respect to the blastogenic response to Con A of Wistar Furth (WF) rats infected by the Y strain of Trypanosoma cruzi (T. cruzi). Enhancement of blastogenesis of normal splenocytes was observed at a concentration of 10(3) M. However, the splenocytes from infected animals responded to concentrations of CIM ranging from 10(-8) to 10(-3) M. The mitogenic response to Con A of cells from infected animals was restored in the presence of CIM. The results show that CIM modulates the "in vitro" proliferative response of cells from T. cruzi-infected rats and suggest an immunoregulatory role of histamine and/or of cells that express H2 receptors in this infection.
