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


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.


CONCLUSIONS
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.
Koval'chuk
L V
LV
Khoreva
M V
MV
Nikonova
A S
AS
Grechenko
V V
VV
Agapov
M A
MA
Indarokov
V A
VA
Leonenko
I V
IV
Gorskiĭ
V A
VA
Gracheva
L A
LA
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007275:Injections, Intravenous; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D019283:Pancreatitis, Acute Necrotizing / Q000188:drug therapy / Q000276:immunology*; D010894:Piroxicam / Q000008:administration & dosage / Q000031:analogs & derivatives*; D051193:Toll-Like Receptors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D010894:Piroxicam; C059451:lornoxicam