Design of iodine-lithium-alpha-dextrin liquid crystal with potent antimicrobial and anti-inflammatory properties.

An ideal antimicrobial should be not toxic and possess board spectrum antiviral, antibacterial, antifungal activity, excluding resistance and should affect pathogen-mediated damage of host physiology including immune, nervous and endocrine systems. With the purpose of a combination of nonspecific antimicrobial action of molecular and ionized iodine with systemic immune-modulating property of the negatively charged polysaccharides a complex drug of iodine and lithium on a template of a alpha-dextrin liquid crystal was designed. The physicochemical model of iodine-lithium-alpha-dextrin (ILalphaD) is based on the human blood and the stereochemistry of moving equilibred systems of dynamically balanced organic polymers conformation complexed with the iodine and lithium molecules. Here we reviewed the antibacterial, antiviral, immune-modulating and anti-inflammatory mechanisms in vivo and in vitro as well as pharmacokinetics, metabolism, chronic toxicity, cumulative properties, embryo toxicity and carcinogenicity of ILalphaD. Clinical efficacy, tolerability and safety of ILalphaD monotherapy have been evaluated in HIV-infected patients, administered intravenously for a total of 12 infusions in 4 cycles. ILalphaD therapy contributes to anti-HIV and anti-inflammatory effects, resolution of dermatological and neurological pathology and dramatically improves the quality of life reflecting on enhanced treatment adherence. ILalphaD appears to be safe and perspective for an adjuvant therapy of bacterial and viral infections, including HIV/AIDS, hypothyroid, autoimmune and inflammatory diseases for controlling pathogen production from infected cells, immune response, inflammation and metabolism.

Hypothalamic proline-rich polypeptide is a regulator of oxidative burst in human neutrophils and monocytes.

OBJECTIVE: The effects of proline-rich polypeptide (PRP) isolated from neurosecretory granules of bovine neurohypophysis produced by nuclei supraopticus and paraventricularis on phagocytosis, bacterial intracellular killing and oxidative burst induction in normal human cells and inflammatory cells from patients with Behçet's disease (BD), i.e. peripheral blood neutrophils and monocytes, were investigated. METHODS: Intracellular killing of Staphylococcus aureus by neutrophils and monocytes of normal controls and BD patients, phagocytic activity as well as spontaneous and N-formyl-Met-Leu-Phe (fMLP)- or phorbol 12-myristate 13-acetate (PMA)-induced activation of their respiratory burst were determined by quantitative flow cytometry using highly specific fluorescence probes. RESULTS: PRP does not affect human peripheral blood neutrophil and monocyte phagocytosis but dramatically enhances spontaneous or fMLP- and PMA-induced oxidative burst as well as the intracellular killing of S. aureus. PRP induced the upregulation of the spontaneous or fMLP- and PMA-induced oxidative burst in normal PMNs and monocytes; the number of inflammatory BD cells did neither increase further nor undergo spontaneous or PMA-stimulated oxidative burst. In BD patients, increased spontaneous production of reactive oxygen intermediates (ROIs) by neutrophils and monocytes is characterized by impaired intracellular protein-kinase-C (PKC)-dependent oxidative burst regulation as well as over-regulation of chemotaxis/inflammation-mediated respiratory burst induction. PRP restores rather the impaired intracellular PKC-dependent regulation of ROI production in inflammatory diseased cells than the chemotaxis/induction of the inflammation-mediated respiratory burst. CONCLUSION: We demonstrated the regulatory role for PRP on oxidative burst in neutrophils and monocytes from normal controls and BD patients. Our results suggest that PRP differentially affects both chemotaxis- and PKC-dependent oxidative burst in normal and inflammatory cells from patients.

Hypothalamic proline-rich polypeptide is an oxidative burst regulator.

The AGAPEPAEPAQPGVY proline-rich polypeptide (PRP) was isolated from neurosecretory granules of the bovine neurohypophysis; it is produced by N. supraopticus and N. paraventricularis. PRP possesses immune-modulating activity, preventing the death of Gram-negative bacteria-infected mice. Here we show that PRP does not affect human peripheral blood neutrophlis and monocytes phagocytosis but dramatically enhances spontaneous or fMLP- and PMA-induced, and also phagocytosis-dependent, oxidative burst. We demonstrated the regulatory role of PRP on the oxidative burst induction of normal and relapsing inflammatory disease (Behcet's disease and familial Mediterranean fever) neutrophils and monocytes. Our results suggest a previously undescribed role for the hypothalamic peptide within primary activated neutrophils and monocytes, since we provide evidence that PRP can differentially regulate both chemotaxis- and phagocytosis-dependent oxidative burst in normal and inflammatory disease effector cells.