In Vitro Demonstration of Drug-Reagent Interactions Among Commonly Used Parenteral Drugs in Cardiology.

BACKGROUND: Drug-drug interactions are undesirable, as they reduce drug bioavailability. Drug-reagent interactions in biochemical tests may directly affect the accuracy of test results. OBJECTIVE: The aim of the present study was to investigate the impact of drug-reagent interactions of drugs used in cardiology on different cardiac markers (troponin I, Nt-proBNP, CK-MB mass, CK, AST, and LDH) and the D-dimer test. METHODS: Eleven drugs (enoxaparin, tirofiban hydrochloride monohydrate, diltiazem, glyceryl trinitrate, metoprolol, epinephrine, heparin sodium, atropine sodium, furosemide, norepinephrine tartrate, and amiodarone HCl) were tested in an interference study. The interference protocol was applied to the control material of troponin I, CK-MB mass, Nt-proBNP, CK, AST, LDH tests with 11 different drugs and performed with analyzers. Cardiac Markers Plus Control (Bio-Rad, Irvine, CA, USA; Lot: 23662) materials were used to assess the impact of drug-reagent interactions on the accuracy of tests of cardiac markers based on immunoassay methods. The bias rate, defined as the extent of deviation from the target value (bias %), in the interference study was calculated in each test. RESULTS: For all 11 drugs, positive interference in the range of 43.58% to 130.06% occurred in the CK-MB mass test, whereas positive interference in the range of 11.98% to 107.44% occurred in the troponin I test. All the drugs, except enoxaparin sodium, led to negative interference in the range of - 84.21 to -29.6% in the Nt-proBNP test. In the D-dimer test, amiodarone HCl and diltiazem caused interference (122.87% and 28.08%, respectively). The percentage of interference caused by the other drugs ranged from -1.27% to 11.44%. Minimal deviations in the target values (between -3.31% and 3.86%) were observed in the CK, AST, and LDH tests measured using spectrophotometric methods. CONCLUSION: Parenteral drugs used in cardiology can significantly interfere with troponin I, CK-MB mass, Nt-proBNP, and D-dimer tests in the analytical phase because of drug-reagent interactions. Minimal deviations in the CK, AST, and LDH tests were observed using spectrophotometric methods. Thus, changes in test results may be due to drug interference rather than the treatment itself. Clinicians should consider the possibility of drug interference in cases of doubtful cardiac test results that do not comply with the diagnosis.

Fingolimod Alters Tissue Distribution and Cytokine Production of Human and Murine Innate Lymphoid Cells.

Sphingosine-1 phosphate receptor 1 (S1PR1) is expressed by lymphocytes and regulates their egress from secondary lymphoid organs. Innate lymphoid cell (ILC) family has been expanded with the discovery of group 1, 2 and 3 ILCs, namely ILC1, ILC2 and ILC3. ILC3 and ILC1 have remarkable similarity to CD4+ helper T cell lineage members Th17 and Th1, respectively, which are important in the pathology of multiple sclerosis (MS). Whether human ILC subsets express S1PR1 or respond to its ligands have not been studied. In this study, we used peripheral blood/cord blood and tonsil lymphocytes as a source of human ILCs. We show that human ILCs express S1PR1 mRNA and protein and migrate toward S1P receptor ligands. Comparison of peripheral blood ILC numbers between fingolimod-receiving and treatment-free MS patients revealed that, in vivo, ILCs respond to fingolimod, an S1PR1 agonist, resulting in ILC-penia in circulation. Similarly, murine ILCs responded to fingolimod by exiting blood and accumulating in the secondary lymph nodes. Importantly, ex vivo exposure of ILC3 and ILC1 to fingolimod or SEW2871, another S1PR1 antagonist, reduced production of ILC3- and ILC1- associated cytokines GM-CSF, IL-22, IL-17, and IFN-γ, respectively. Surprisingly, despite reduced number of lamina propria-resident ILC3s in the long-term fingolimod-treated mice, ILC3-associated IL-22, IL-17A, GM-CSF and antimicrobial peptides were high in the gut compared to controls, suggesting that its long term use may not compromise mucosal barrier function. To our knowledge, this is the first study to investigate the impact of fingolimod on human ILC subsets in vivo and ex vivo, and provides insight into the impact of long term fingolimod use on ILC populations.