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Published on: February 11, 2009
The effect of interleukin-6 on L-selectin levels on polymorphonuclear leukocytes
Tatsushi Suwa1, James C Hogg, Kevin B Quinlan
1McDonald Research Laboratory and iCAPTURE Centre, University of British Columbia, St. Paul's Hospital, Vancouver, British Columbia, Canada V6Z 1Y6.
Abstract:
Interleukin-6 (IL-6) shortens the transit time of polymorphonuclear leukocytes (PMN) through the marrow and accelerates their release into the circulation. In contrast to other inflammatory stimuli, this response is associated with a decrease in L-selectin levels on circulating PMN. The present study was designed to determine the effect of IL-6 on L-selectin levels of PMN in rabbits. Recombinant human IL-6 (2 microg/kg) caused a decrease in L-selectin levels on circulating PMN 3 to 12 h after treatment (P < 0.05). L-selectin levels decreased on PMN already in the circulation for up to 4 h (P < 0.05), on PMN released from the marrow posttreatment for up to 12 h (P < 0.01) and on PMN in the marrow for up to 6 h (P < 0.05) after IL-6 treatment. We conclude that IL-6 decreases L-selectin levels on circulating PMN by demarginating PMN with low levels of L-selectin and by releasing PMN from the marrow with low levels of L-selectin. We postulate that this prolonged downregulation of L-selectin on circulating PMN could influence their recruitment into inflammatory sites.
Insights
Interleukin-6 (IL-6) reduces L-selectin levels on circulating polymorphonuclear leukocytes (PMN). This immune response involves demargination and accelerated release of PMN with lower L-selectin from the marrow.
Area of Science:
- Immunology
- Hematology
Background:
- Interleukin-6 (IL-6) influences polymorphonuclear leukocyte (PMN) kinetics and release from bone marrow.
- IL-6's effect on PMN L-selectin levels differs from other inflammatory stimuli.
Purpose of the Study:
- To investigate the impact of IL-6 on L-selectin expression in rabbit PMN.
- To elucidate the mechanisms by which IL-6 affects PMN L-selectin levels.
Main Methods:
- Administration of recombinant human IL-6 to rabbits.
- Quantification of L-selectin levels on circulating and marrow PMN over time.
Main Results:
- IL-6 treatment significantly decreased L-selectin levels on circulating PMN from 3 to 12 hours post-treatment.
- L-selectin levels were reduced on PMN in circulation (up to 4 hours) and newly released from marrow (up to 12 hours).
- PMN within the bone marrow also showed decreased L-selectin levels for up to 6 hours after IL-6 administration.
Conclusions:
- IL-6 downregulates L-selectin on circulating PMN through demargination and enhanced marrow release.
- The sustained reduction in PMN L-selectin by IL-6 may impact leukocyte recruitment to inflammatory sites.
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