Attenuation of proinflammatory response by recombinant human IL-10 in human endotoxemia: effect of timing of recombinant human IL-10 administration.
To determine the effects of IL-10 on cytokine and granulocyte responses during endotoxemia, two groups of eight healthy male volunteers were challenged with endotoxin (4 ng/kg) on two occasions, once in combination with placebo injection, and once in conjunction with i.v. administered recombinant human IL-10 (rhIL-10) (25 microg/kg). In group 1, rhIL-10 was administered 2 min before endotoxin challenge; in group 2, the intervention was delayed for 1 h after endotoxin administration. rhIL-10 pretreatment reduced the LPS-induced rises in temperature and release of TNF, IL-6, IL-8, and IL-1 receptor antagonist. Endotoxin-induced granulocyte accumulation in lungs, as determined by dynamic granuloscintigrams, was prevented by rhIL-10 pretreatment, whereas granulocyte recruitment in liver and spleen was only modestly reduced. In addition, granulocyte degranulation, as measured by plasma elastase/alpha1-antitrypsin complexes, was blunted significantly by rhIL-10 pretreatment. Post-treatment with rhIL-10 did not influence LPS-induced temperature responses, cytokine release, or granulocyte degranulation. Both rhIL-10 pretreatment and post-treatment reduced LPS-induced cortisol levels. These results indicate that pretreatment with rhIL-10 reduces endotoxin-induced febrile responses, cytokine responses, and granulocyte accumulation in lungs, while in this acute model post-treatment with rhIL-10 exerts limited anti-inflammatory effects.
Pajkrt
D
D
Department of Experimental Internal Medicine, University of Amsterdam, The Netherlands.
Camoglio
L
L
Tiel-van Buul
M C
MC
de Bruin
K
K
Cutler
D L
DL
Affrime
M B
MB
Rikken
G
G
van der Poll
T
T
ten Cate
J W
JW
van Deventer
S J
SJ
D000328:Adult; D004311:Double-Blind Method; D019446:Endotoxemia / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007275:Injections, Intravenous; D016753:Interleukin-10 / Q000008:administration & dosage*; D008297:Male; D011994:Recombinant Proteins / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome
D011994:Recombinant Proteins; D016753:Interleukin-10