Therapy with TLR7 agonists induces lymphopenia: correlating pharmacology to mechanism in a mouse model.

Background And Objective: Synthetic TLR7 agonists have been proposed as oral replacements for interferonα (IFNα) therapy in the treatment of hepatitis C virus infection. However, adverse effects, such as lymphopenia and cardiovascular irregularities, have been observed in the clinical following treatment with TLR7 agonists. We wished to understand and characterise the relationship between TLR7 agonism and adverse effects.

Uptake, efficacy, and systemic distribution of naked, inhaled short interfering RNA (siRNA) and locked nucleic acid (LNA) antisense.

Antisense oligonucleotides (ASOs) and small interfering RNA (siRNA) promise specific correction of disease-causing gene expression. Therapeutic implementation, however, has been forestalled by poor delivery to the appropriate tissue, cell type, and subcellular compartment. Topical administration is considered to circumvent these issues.

A subpopulation of human B lymphocytes can express a functional Tissue Factor in response to phorbol myristate acetate.

Tissue Factor (TF,CD142) is a transmembrane glycoprotein that belongs to the cytokine receptor superfamily. This multifunctional protein is constitutively present in most tissues. Among circulating blood cells, TF expression is known to be restricted to monocytes which do not constitutively produce TF but express TF in response to various stimuli.