[Inhibition of nimodipine on production of proinflammatory by Kupffer cells in severe burned rats].
OBJECTIVE
To study whether nimodipine, a dihydropyridine-type calcium channel blocker, can inhibit the production of interleukin-1beta(IL-1beta), interleukin-6(IL-6) by Kupffer cells(KC) and down-regulate its level of plasma after severe burn injury.


METHODS
KC of normal rats were isolated with portal vein catheter, intrahepatic digestion and density gradient centrifugation. Intracellular calcium concentration ([Ca2+]i) in individual KC after stimulated with postburn serum was assessed fluorometrically with microspectrofluorimeter. Level of IL-1beta and IL-6 in the supernatant of KC cultured with postburn serum were detected by enzyme-linked immunosorbent assay(ELISA). SD rats underwent 30% total body surface area(TBSA) full thickness burn 6 hours later, KCs was isolated and their mRNA were extracted. Level of IL-1beta mRNA and IL-6 mRNA were detected by ribonuclease protection assay(RPA). Levels of plasma IL-1beta and IL-6 were also detected. Role of nimodipine on above-mentioned effects were observed.


RESULTS
Compared with that of control group, levels of [Ca2+]i of KCs and IL-1beta and IL-6 supernatant in burn group increased significantly(all P<0.01). At present of 1 micromol/L nimodipine, however, the [Ca2+]i, IL-1beta, IL-6 values decreased significantly(all P<0.01). The level of plasma cytokines and KC mRNA in burn group also increased significantly. After intravenously injection with nimodipine (40 microg x kg(-1) x h(-1)), the numerical values decreased significantly(all P<0.01).


CONCLUSIONS
Kupffer cells of rats are activated to secret IL-1beta and IL-6 after severe burn injury and this process is realized through calcium ion signal transduction channel. Nimodipine can inhibit IL-1beta and IL-6 production of KC by preventing its mRNA transcription, down-regulating its level of plasma.
Wang
Guang-yi
GY
The Burn Department, Changhai Hospital, Shanghai 200433, China.
Zhu
Shi-hui
SH
Tang
Hong-tai
HT
Ge
Sheng-de
SD
Xia
Zhao-fan
ZF
D000818:Animals; D002056:Burns / Q000378:metabolism*; D002478:Cells, Cultured; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007728:Kupffer Cells / Q000187:drug effects* / Q000378:metabolism*; D009553:Nimodipine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D053583:Interleukin-1beta; D015850:Interleukin-6; D009553:Nimodipine