Diminished cytokine signalling against bacterial components in mononuclear leucocytes from ulcerative colitis patients after leukocytapheresis

Abstract

SummaryInfiltration by circulating inflammatory cells is a prominent local inflammatory feature of ulcerative colitis (UC). Several trials have suggested that leukocytapheresis by filtration can benefit patients with active UC. We investigated how this therapy might modulate the inflammatory response. Patients with active UC who were beginning repeated filtration leukocytapheresis were studied. Mononuclear cell preparations were obtained from blood before and after the first treatment, and expression of cytokine signalling components and the cell-proliferative response were analysed in vitro . Leukocytapheresis reduced lipopolysaccharide-induced production of proinflammatory cytokines (interleukin-1, -6, -8 and tumour necrosis factor-a a a a , P < < < < 0·05 for all) and activation of intracellular signalling components (nuclear factor-k k k k B, mitogen-activated protein kinases, and signal transducer and activator of transcription-3), as well as surface expression of toll-like receptor-4 ( P < < < < 0·05) in mononuclear cells. The therapy also reduced the cell-proliferative response by mononuclear cells stimulated with sonicated bacterial preparations from autologous intestine ( P < < < < 0·05). These results indicate that activated mononuclear cells in the peripheral blood of patients with active UC are removed by leukocytapheresis and replaced by cells with a lower activation status. This replacement may partly explain the therapeutic benefit.

Leukocytapheresis for the treatment of active pouchitis: a pilot study

“…[21][22][23] Furthermore, patients who develop pouchitis show higher activation of signal transducer and activator of transcription (STAT)-1, a transcription factor that activates genes involved in infl ammatory and immune responses, in the pouch mucosa. 24 LCAP may reduce infl ammation via the removal of activated leukocytes that produce infl ammatory cytokines such as interleukin (IL)-1, IL-6, and TNF-α, [25][26][27] and the removal of activated platelets that can produce active oxygen. [28][29][30] Standard medical therapy for pouchitis attempts to interfere with luminal bacteria using antibiotics or probiotics.…”

Safety and tolerability of a modified filter‐type device for leukocytapheresis using ACD‐A as anticoagulant in patients with mild to moderately active ulcerative colitis. Results of a pilot study

“…Additional mechanisms including the triggering of immunomodulatory or regulatory processes have been suggested to be operative [3,4,[15][16][17][18]. Moreover, the release of biologically active substances from the cells adsorbed in the apheresis columns has also been described [19,20].…”

“…We chose to analyze the following immunoregulatory markers, which could be adsorbed or released in the lines or in the apheresis filter (column): CD30L (regulatory ligand with described importance for IBD [24]), IL-1receptor-antagonist (earlier reported to be released in Adacolumn [16]) and LL-37 (an antimicrobial and regulatory peptide mainly contained in granulocytes [25,26]). …”

Mechanisms Underlying the Effects of Leukocyte Apheresis with a Fiber Filter in a Rat Model of Dextran Sulfate Sodium-Induced Colitis

“…LCAP also blocked mononuclear cell activity, as assessed by proliferative responses and inflammatory cytokine production. In patients with UC, we previously found that LCAP inhibited cytokine production in LPS-stimulated PBMCs through reducing toll-like receptor-4 expression and the subsequent activation of NF-jB and mitogen-activated protein kinases [21]. LCAP also reduces cytokine-induced production of inflammatory cytokines from PBMCs [22].…”