[Recognition receptors of innate immunity (NLR, RLr, and CLR)].

Current concepts of recognition receptors of innate immunity (pattern-recognition receptors, PRR) are discussed in the review. Structural and functional features of receptors from the families NOD-like receptors (NLRs), RIG-like receptors (RLRs), and C-type lectin-like receptors (CLRs) are described. These receptors are found on cell surface or in cytoplasm, and also could be presented in organism in secretory form. Data on exogenous and endogenous ligands, signal transduction mechanisms that induce production of proinflammatory cytokines, chemokines, and antimicrobial petides are summarized in the review. Special attention is paid to family of NLR receptors, which are involved in generation and activation of multimeric protein complex called an inflammasome. Activation of inflammasome leads to generation of active forms of proinflammatory cytokines belonging to IL-1 family (IL-1beta, IL-18, and IL-33) from their precursor peptides due to effect of caspase-1. Data regarding involvement of innate immunity receptors in development and pathogenesis of various diseases are presented.

[Toll-like receptor-mediated functional activity of mononuclear cells in children with neutropenia].

AIM: To study the Toll-like receptor (TLR)-mediated functional activity of peripheral blood mononuclear cells (PBMC) from children with different forms of neutropenia. MATERIALS AND METHODS: TLR-mediated functional activity of PBMC was evaluated by production of proinflammatory cytokines--TNF alpha and IFN alpha. Ligands for TLR1/2, TLR 2/6, TLR4, TLR5, and TLR9 were used to stimulate TNF alpha production by PBMC from healthy children and children with neutropenia. Ligands for TLR3, TLR4, TLR7, TLR7/8, TLR8, and TLR9 were used to induce production of IFN alpha. Levels of TNF alpha and IFN alpha were measured in PBMC supernatants by ELISA. The group of patients with neutropenia included 9 children with immune neutropenia and 3 children with congenital neutropenia. Control group consisted of 12 healthy children of the same age range. RESULTS: It was revealed that TLR2, TLR4, and TLR5 ligands have enhanced stimulating effect on TNF alpha production by PBMC of children with congenital neutropenia and had no effect on PBMC of children with immune neutropenia. Children with immune neutropenia are characterized by significantly increased IFN alpha production induced by ligands of TLR3, TLR8, and TLR9. CONCLUSION: Revealed changes of TLR-mediated functional activity of PBMC from children with various forms of neutropenia may play significant role in development and course of infections in these patients.

[Corrective effect of cyclooxygenase inhibitor on functional status of mononuclear cells expressing Toll-like receptors].

AIM: To study the influence of the COX inhibitor--lornoxicam (LX)--on Toll-like receptor (TLR)-mediated production of proinflammatory and anti-inflammatory cytokines by peripheral blood mononuclear cells (PBMC) from healthy subjects and patients with acute pancreatitis (AP) in vitro. MATERIALS AND METHODS: Cytokine production by PBMC of healthy donors was stimulated by TLR1/2 ligand peptidoglycan (PG) and TLR4 ligand lypopolysaccharide (LPS) in presence of LX. Levels of cyotokines (IL-1beta, IL-6, IL-8, IL-10, IL-12, and TNFalpha) were measured by ELISA. Group of patients with acute pancreatitis of toxic etiology included 11 subjects: patients from main group received combined therapy supplemented with NSAID from the oxicam class--LX; patients who received only standard basic treatment formed comparison group. RESULTS: It was found that in vitro LX inhibits production of both proinflammatory and anti-inflammatory cytokines by PBMC of healthy subjects mediated by ligands of TLR1/2 and TLR4. Maximal inhibitory effect of LX was observed when cytokine production was induced through TLR1/2. Patients with AP demonstrated increased production of TNFalpha induced by TLR1/2 and TLR4 ligands. CONCLUSION: LX inhibits TLR-mediated production of both proinflammatory (IL-1, IL-6, IL-8, IL-12, TNFalpha) and anti-inflammatory (IL-10) cytokinesby PBMC of healthy subjects in vitro. Treatment with LX in patients with AP results in diminished effector function of TLR1/2 and TLR4 already during 1st day of the illness and normalization of these indices by 6th day.