ABSTRACT
AIMS: A new L-asparaginase produced by Streptomyces ansochromogenes UFPEDA 3420 actinobacteria was used in this study against human lymphocyte cultures to evaluate the immunological profile induced by this enzyme. METHODS AND RESULTS: Cultures of lymphocytes were stimulated with S. ansochromogenes L-asparaginase, and cytotoxicity, cell viability, cell stimulation and cytokine production were analysed. This new S. ansochromogenes L-asparaginase induced activation and proliferation of the TCD8+ lymphocyte subset and produced higher TNF-α, IFN-γ, IL-2 and IL-10 levels in a 24-h assay. CONCLUSION: Streptomyces ansochromogenes L-asparaginase is a promising molecule to be used in in vivo models and to deepen preclinical tests against acute lymphoblast leukaemia. SIGNIFICANCE AND IMPACT OF STUDY: L-asparaginase is an indispensable component of the chemotherapeutic treatment of acute lymphoblast leukaemia (ALL) and acute myeloid leukaemia (AML). Currently, drugs such as Asparaginase® , Kidrolase® , and Elspar® and Erwinase® are efficient against leukemic disease, but promote immunosuppression and other side effects in human organisms. Our purified S. ansochromogenes L-asparaginase showed promissory results inducing, in vitro, higher immunostimulation in human PBMC, especially in T CD8+ lymphocyte subsets.
Subject(s)
Asparaginase/pharmacology , CD8-Positive T-Lymphocytes/drug effects , Lymphocyte Activation/drug effects , Streptomyces/enzymology , Th1 Cells/drug effects , Asparaginase/isolation & purification , Asparaginase/toxicity , CD8-Positive T-Lymphocytes/immunology , Humans , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/immunologyABSTRACT
The pathology of schistosomiasis is associated with the formation of granulomas, and this process is associated with liver fibrosis. Studies indicate that Th1 cytokines reduce fibrosis in schistosomiasis, while Th2 cytokines play a part in the progression of fibrosis, and IL-13 has a critical role in this process. The IL-13Rα2 receptor, known as a 'receptor antagonist' binds with high affinity to IL-13, and studies have identified that this plays a part in reducing fibrosis and the size of granulomas. The objective of this study was to evaluate the function of IL-13Rα2 and cellular immune response in hepatic fibrosis. A negative correlation between IL-13Rα2 and IL-13 was found, suggesting an increase in cytokine in early fibrosis. Initially, a negative correlation between IFN-γ and IL-13 was found in patients without fibrosis, and subsequently, this correlation was found to be positive in patients with severe fibrosis, thereby highlighting a new mechanism for regulating the progress of periportal fibrosis. There was a positive correlation between the profiles of Th1 and Th2 cytokines, suggesting the presence of both responses, thus regulating the disease. The results contribute to a better understanding of the immune mechanisms that control the process of hepatic fibrogenesis in schistosomiasis in humans.
