Modulating effects of nonselective and selective phosphodiesterase inhibitors on lymphocyte subsets and humoral immune response in mice.
Journal Title: Pharmacological Reports - Year 2010, Vol 62, Issue 6
Abstract
Phosphodiesterase (PDE) inhibitors can regulate the activity of immune cells by increasing intracellular levels of cyclic nucleotides. The aim of this study was to determine the effects of milrinone, a selective PDE3 inhibitor, sildenafil, a selective PDE5 inhibitor, and aminophylline, a nonselective PDE inhibitor, on lymphocyte subsets and humoral immune response in mice when administered in vivo. Aminophylline (20 mg/kg, im), milrinone (1 mg/kg, im) or sildenafil (1 mg/kg, po) were administered to mice either once or five times at 24 h intervals. Some mice were immunized with a sheep red blood cell (SRBC) suspension administered ip either 2 h after the single dose or 2 h after the second of the five doses. In non-immunized mice treated five times with PDE inhibitors, the subsets of T lymphocytes in the thymus and T and B lymphocytes in the spleen and mesenteric lymph nodes were determined 12, 24 or 72 h after the last dose. The humoral immune response was determined on days 4, 7 and 14 after SRBC injection in SRBC-immunized mice treated with PDE inhibitors. A modulating effect of the drugs on lymphocyte subpopulations was observed. The greatest impact was observed in splenocyte subpopulations, and resulted in decreased percentages of B cells (CD19(+)) and increased percentages of T cells (CD3(+), CD4(+), CD8(+)). No effect or slight influence of the drugs on anti-SRBC hemagglutinins was observed, but the number of plaque-forming splenocytes was increased. The drugs under investigation did not show a significant immunosuppressive effect.
Authors and Affiliations
Marianna Szczypka, Bożena Obmińska-Mrukowicz
ERK signalling pathway is not involved in PSA-NCAM-dependent alterations of hippocampal plasticity evoked by CB1 receptor activation.
The present study investigated the potential role of the extracellular signal-regulated kinase (ERK) pathway in the alternation of polysialylated neural cell adhesion molecule (PSA-NCAM) expression and proliferation rate...
Delta opioid receptors contribute to the cardiorespiratory effects of biphalin in anesthetized rats.
Biphalin expresses almost equal affinity for μ- and δ-opioid receptors. The aim of this study was to delineate a possible role of δ-opioid receptors in the cardio-respiratory effects of systemic injection of biphalin in...
Serum kynurenic acid positively correlates with cardiovascular disease risk factor, homocysteine: a study in stroke patients.
KYNA, an antagonist of ionotropic glutamate receptors and alpha7 nicotinic receptors, has been found as well in the brain as in the periphery. The altered metabolism of KYNA, especially its deficiency, can lead to the en...
Effects of N-(morpholinomethyl)-p-isopropoxyphenylsuccinimide on the protective action of different classical antiepileptic drugs against maximal electroshock-induced tonic seizures in mice.
Background: The aim of this study was to determine the effects of N-(morpholinomethyl)-p-isopropoxy-phenylsuccinimide (MMIPPS) on the protective action of four classical antiepileptic drugs (AEDs: carbamazepine [CBZ], ph...
Mechanisms and pharmacology of diabetic neuropathy - experimental and clinical studies.
Neuropathic pain is the most common chronic complication of diabetes mellitus. The mechanisms involved in the development of diabetic neuropathy include changes in the blood vessels that supply the peripheral nerves; met...