Basic inflammatory indices and chosen neutrophil receptors expression in chronic haemodialysed patients.

AIM OF THE STUDY: End stage renal disease (ESRD) patients on chronic haemodialysis (HD) are immuno-compromised and prone to infection. Toll-like receptors (TLRs) play a role as both primary sensors of pathogen invasion and activators of inflammatory reaction. To test if the immune impairment in HD patients is connected with the defective expression of the neutrophil TLRs, we aimed to examine their expression and chosen inflammatory indices. MATERIAL AND METHODS: We tested CD14, TLR4, and TLR9 expressions on neutrophils using flow cytometry. Soluble CD14, C-reactive protein (CRP), and mannose-binding lectin (MBL) concentrations were tested using the ELISA method in 31 ESRD patients on chronic haemodialysis programs and in 17 healthy control subjects. RESULTS: Neutrophil TLR4 and TLR9 expressions did not differ significantly compared to the controls. The ESRD patients had markedly increased CRP and sCD14 levels alongside decreased MBL concentrations and neutrophil CD14 expression. The TLR4 expression correlated well with both TLR9 and CD14 neutrophil expressions; however, the increased CRP in the blood did not correlate with the MBL concentration or TLR expression. CONCLUSIONS: The chronic program of haemodialysis and biochemical disorders in ESRD patients result in a low-grade chronic inflammation with no significant impact on the expression of neutrophil TLR4 and TLR9.

Immunoregulatory action of melatonin. The mechanism of action and the effect on inflammatory cells.

Literature data indicate a significant immunoregulatory role of melatonin. Melatonin exerts an effect directly affecting leucocytes bearing specific melatonin receptors or indirectly by means of melatonin regulating other hormones, opioids or cytokines. Despite numerous experiments, the influence of the hormone on the immune system is still controversial. Melatonin affects the immune response acting as both an activator and an inhibitor of the inflammatory process. The hormone acts as an "immunological buffer" activating impaired immunity in immunosuppression, chronic stress or old age as well as suppressing overreaction of the immune system. Melatonin mediates between neurohormonal and immune systems by means of the immune-pineal axis acting as a negative feedback mechanism. The axis connects development of the immune reaction with pineal activity and melatonin secretion induced by inflammatory mediators. The seasonal and circadian fluctuation of the melatonin level and the fluctuation related changes of the immune parameters can be responsible for some autoimmune and infectious diseases. In spite of that, there is a growing number of papers suggesting considerable therapeutic potential of melatonin in inflammatory disease treatment. This paper presents well-systematized information on the mechanism of melatonin action and its influence on cells involved in the inflammatory process - neutrophils and monocytes.

Cytotoxic Activity of Melatonin Alone and in Combination with Doxorubicin and/or Dexamethasone on Diffuse Large B-Cell Lymphoma Cells in In Vitro Conditions.

Melatonin (MLT), a pineal gland hormone, not only regulates circadian and seasonal rhythms, but also plays an important role in many aspects of human physiology and pathophysiology. MLT is of great interest as a natural substance with anti-cancer activities. The aim of this study was to assess the cytotoxicity and apoptosis of MLT, used alone or in combination with one of the most active anti-cancer drugs, doxorubicin (DOX), and a well-known anti-inflammatory drug, dexamethasone (DEX), on a diffuse large B-cell lymphoma (DLBCL)-derived cell line. The cytotoxicity and cell cycle distribution were measured using propidium iodide staining, while apoptosis was assessed using the annexin-V binding method. Additionally, to elucidate the mechanisms of action, caspase-3, -8, and -9 and a decline in the mitochondrial potential were determined using flow cytometry. MLT inhibited cell viability as well as induced apoptosis and cell cycle arrest at the G0/G1 phase. The pro-apoptotic effect was exerted through both the mitochondrial and caspase-dependent pathways. Furthermore, we observed increased cytotoxic and pro-apoptotic activity as well as the modulation of the cell cycle after the combination of MLT with DOX, DEX, or a combination of DOX + DEX, compared with both drugs or MLT used alone. Our findings confirm that MLT is a promising in vitro anti-tumour agent that requires further evaluation when used with other drugs active against DLBCL.