CORRECTIVE EFFECT OF CYCLOOXYGENASE INHIBITOR ON FUNCTIONAL STATUS OF MONONUCLEAR CELLS EXPRESSING TollLIKE RECEPTORS

Aim. To study the influence of the COX inhibitor - lornoxicam (LX) - on Toll-like receptor (TLR)- mediated production of proinflammatory and antiinflammatory 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-1β, IL-6, IL-8, IL-10, IL-12, and TNFα) 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 TNFα induced by TLR1/2 and TLR4 ligands. Conclusion. LX inhibits TLR-mediated production of both proinflammatory (IL-1, IL-6, IL-8, IL-12, TNFα) and anti-inflammatory (IL-10) cytokines by 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 1 st day of the illness and normalization of these indices by 6 th day.

Toll-like receptors, acute pancreatitis, lornoxicam, cytokines