Lower circulating kisspeptin and primary hypogonadism in men with type 2 diabetes.

INTRODUCTION: Kisspeptin influence on male androgens is partially understood. We aimed to evaluate serum concentrations of kisspeptin among Ghanaian men with type 2 diabetes and to identify related factors that may contribute to altering circulating kisspeptin. METHODS: A cross-sectional, observational study. Sixty persons with type 2 diabetes and 60 nondiabetic controls were included in this study. Blood pressure, body mass index (BMI), kisspeptin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (T), glucose (FBG), glycated haemoglobin (HbA1c) and lipid levels were assessed. RESULTS: Type 2 diabetic men had lower kisspeptin and T concentrations than controls (P = 0.001 for both). Levels of LH and FSH were, respectively, higher in diabetic men compared with their control counterparts (P = 0.003; P = 0.017). There were negative associations within the diabetic group for kisspeptin vs age (r = -0.590, P = 0.0001) and kisspeptin vs BMI (r = -0.389, P = 0.002). Positive associations were also found within the diabetic group for kisspeptin vs T (r = 0.531, P = 0.001), kisspeptin vs LH (r = 0.423, P = 0.001) and kisspeptin vs FSH (r = 0.366, P = 0.004). Lower T (OR = 1.473, P = 0.003) and advancing age (OR = 0.890, P = 0.004) contributed to decreased kisspeptin levels among Ghanaian males with type 2 diabetes. CONCLUSION: Our data demonstrate that circulating kisspeptin and T concentrations are lower among men with type 2 diabetes and highlight the importance of considering kisspeptin concentrations in the management of hypogonadism and type 2 diabetes.

PD-L1 expression is increased in monocyte derived dendritic cells in response to porcine circovirus type 2 and porcine reproductive and respiratory syndrome virus infections.

Host immune system suppression is thought to be crucial in the development of porcine circovirus associated diseases (PCVAD). Many immune suppressive mechanisms have been studied in cases of PCVAD, however, the role of programmed death ligand-1 (PD-L1) during porcine circovirus type 2 (PCV2) infection and PCVAD development has yet to be determined. PD-L1 has become an important research target because of its ability to interfere with effective T-cell activity and proliferation during the course of an immune response. In this study, porcine monocyte derived dendritic cells (MoDC) were infected with different combinations of PCV2 and porcine reproductive and respiratory syndrome virus (PRRSV) and evaluated for expression levels of PD-L1, as well as the expression levels of swine major histocompatibility complexes 1 and 2 (SLA-1 and SLA-2) as a measure of MoDC stimulatory capacity. PD-L1 expression levels were also tested in MoDCs after treatment with interferon alpha (IFN-α) and beta (IFN-ß). The results showed that the expression levels of PD-L1 were increased in PCV2-infected MoDCs, as well as in PCV2 and PRRSV co-infected MoDCs. The MoDCs infected with PRRSV only also showed a strain-dependent increase in PD-L1 expression. Both IFN-α and IFN-ß treatment also increased the expression levels of PD-L1 in MoDCs. SLA-1 and 2 expression levels were increased by PCV2 infection, and altered in the PRRSV, and PCV2+PRRSV co-infected MoDCs in a strain-dependent manner. These results indicate a potential immuno-suppressive role for dendritic cells during PCV2 infection and the development of PCVAD and will be helpful in more fully elucidating the underlying mechanisms leading to clinical PCVAD.

The PD-L1/CD86 ratio is increased in dendritic cells co-infected with porcine circovirus type 2 and porcine reproductive and respiratory syndrome virus, and the PD-L1/PD-1 axis is associated with anergy, apoptosis, and the induction of regulatory T-cells in porcine lymphocytes.

Porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) continue to have a negative economic impact on global swine production operations. Host immune modulations that potentiate disease during PCV2 and/or PRRSV infections are important areas of ongoing research. In this study, we evaluated the expression levels of PD-L1, CD86, and IL-10 in order to phenotype dendritic cells following viral infection with PCV2b and/or PRRSV. The results showed that the inhibitory marker PD-L1 was significantly increased in monocyte derived dendritic cells (MoDC) in both singular PCV2 infection and PCV2/PRRSV co-infections. MoDC expression of stimulatory marker CD86 was significantly increased during singular PCV2 infections, while it was significantly decreased in the treatment groups co-infected with both PCV2 and PRRSV. IL-10 production was highest among MoDCs that were co-infected with PCV2 and PRRSV. These results indicate that dendritic cells develop a regulatory phenotype following PCV2/PRRSV co-infections. We further investigated the role of the PD-L1/PD-1 axis in lymphocyte anergy, apoptosis, and the induction of regulatory T-cells in porcine mononuclear cell populations. Lymphocyte populations with normal PD-1 expression had higher percentages of anergic, apoptotic lymphocytes and CD4(+)CD25(HIGH)FoxP3(+) regulatory T-cells when compared to a PD-1 deficient lymphocyte population. These results implicate the PD-L1/PD-1 axis in negative regulation of lymphocyte responses in pigs.