ATTENUATION OF PROINFLAMMATORY RESPONSE BY RECOMBINANT HUMAN IL-10 INHUMAN ENDOTOXEMIA - EFFECT OF TIMING OF RECOMBINANT HUMAN IL-10 ADMINISTRATION

To determine the effects of IL-10 on cytokine and granulocyte response s during endotoxemia, two groups of eight healthy male volunteers were challenged with endotoxin (4 ng/kg) on two occasions, once in combina tion with placebo injection, and once in conjunction with i.v. adminis tered recombinant human IL-10 (rhIL-10) (25 mu g/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 rele ase of TNF, IL-6, IL-8, and IL-1 receptor antagonist. Endotoxin-induce d granulocyte accumulation in lungs, as determined by dynamic granulos cintigrams, was prevented by rhIL-10 pretreatment, whereas granulocyte recruitment in liver and spleen was only modestly reduced. In additio n, granulocyte degranulation, as measured by plasma elastase/alpha(1)- antitrypsin complexes, was blunted significantly by rhIL-10 pretreatme nt. Post-treatment with rhIL-10 did not influence LPS-induced temperat ure responses, cytokine release, or granulocyte degranulation. Both rh IL-10 pretreatment and post-treatment reduced LPS-induced cortisol lev els. These results indicate that pretreatment with rhIL-10 reduces end otoxin-induced febrile responses, cytokine responses, and granulocyte accumulation in lungs, while in this acute model post-treatment with r hIL-10 exerts limited anti-inflammatory effects.