THE STUDY OF REGULARITIES OF INDUCTION OF IL-8 SYNTHESIS BY NEUTROPHIL DEFENSINS IN VITRO

Abstract. We explored the effects of defensins on IL-8 synthesis in various human cells, including bronchoepithelial cell line A-549, monocytes, monocyte-derived macrophages differentiated in the presence of M-CSF, HU-VEC cells, HEK293 and THP-1 cell lines. HNP at 10-5-10-4М induced IL-8 production and cytotoxicity in serum-less A-549 culture. The addition of serum abrogated the cytotoxicity along with the induction of IL-8 synthesis. Similar effects were observed in HEK293 cell line and HUVEC.The induction of cytotoxicity along with IL-8 production by HNP at 10-5-10-4М was also observed in the serum-less cultures of human monocytes and macrophages. However, monocytes and macrophages retained HNP-induced production of IL-8 after the addition of serum, while cytotoxic effect of HNP was completely inhibited. The data imply a specific interaction of alpha-defensins with some membrane receptors of monocytes and macrophages that leads to the induction of IL-8 and might also occur in vivo.</p

THE LEVELS OF SOLUBLE RECEPTOR OF TUMOR NECROSIS FACTOR P55, TNF, NEUTROPHIL-DERIVED ALPHA-DEFENSINS AND BOTH ISOFORMS OF INTERLEUKIN-8 IN THE BLOOD AND CEREBROSPINAL FLUID (CSF) FROM CHILDREN WITH GENERALIZED FORMS OF MENINGOCOCCAL INFECTION

<strong>Abstract. </strong>Generalized forms of meningococcal infection (GFMI) are usually accompanied with apparent symptoms of systemic inflammatory response (SIRS). Systemic production of inflammatory cytokines, their accumulation in circulating blood and action on various organs and tissues represent a crucial constituent of SIRS. Current study explored the levels of soluble receptor of tumor necrosis factor (TNF) p55, TNF, neutrophil-derived alpha-defensins (HNP) and both isoforms of Interleukin-8 (IL-872 and IL-877) in blood and cerebrospinal fluid (CSF) from children with GFMI. The levels of cytokines were estimated using "sandwich" enzyme-linked immunoassays emploing monoclonal antibodies to corresponding cytokines that were previously developed in our laboratory. It was shown that the levels of p55 in the blood correlated with severity of SIRS and GFMI, while the levels of HNP (human neut rophil peptides) in CSF may serve as more sensitive marker of inflammation since HNP levels decreased more rapidly during a recovery of disease comparing to p55. Elevated levels of IL-877 during GFMI correlated with the levels of p55 (correlation coefficient 0,142, р = 0,489), whereas no correlation between the levels of p55 and IL-872 was revealed

Patient and clinical characteristics.

<p>*Values shown are medians (inter-quartile range) with superscript numbers indicating days in addition to gestation in weeks; ^∧ values shown are numbers of infants (percentage of total in group).</p><p>Patient and clinical characteristics.</p

Neutrophil chemotaxis to preterm BALF.

<p>Chemotaxis of adult human neutrophils to pooled BALF from BPD infants after incubation for 60 min. Conditions are detailed on the x-axis while concentration of neutrophils (cells/ml) are expressed on the y-axis. Bars are at means (± SEM) of three independent experiments, each done in triplicate. Conditions were compared by one-way ANOVA with Dunnet's correction, comparing against a control column (BALF only). (*** = p<0.001).</p