In vivo induction of interleukin 10 by anti-CD3 monoclonal antibody or bacterial lipopolysaccharide: differential modulation by cyclosporin A.
We investigated the in vivo effects of cyclosporin A (CsA) on the production of interleukin (IL) 10, a cytokine with major immunosuppressive properties. To elicit IL-10 production in vivo, BALB/c mice were injected either with the anti-mouse CD3 145-2C11 monoclonal antibody (mAb) (25 micrograms) or with bacterial lipopolysaccharide (LPS) (20 micrograms). A systemic release of IL-10 was observed in both models, IL-10 serum levels reaching 1.60 +/- 0.32 U/ml (mean +/- SEM) and 0.67 +/- 0.09 U/ml 6 h after injection of 145-2C11 mAb and LPS, respectively. Experiments in nude mice indicated that T cells are involved in the induction of IL-10 by anti-CD3 mAb, but not by LPS. Pretreatment with CsA (total dose: 50 mg/kg) before injection of 145-2C11 mAb completely prevented the release of IL-10 in serum as well as IL-10 mRNA accumulation in spleen cells. In contrast, CsA markedly enhanced LPS-induced IL-10 release (IL-10 serum levels at 6 h: 8.31 +/- 0.43 vs. 0.71 +/- 0.15 U/ml in mice pretreated with CsA vehicle-control, p < 0.001), as well as IL-10 mRNA accumulation in spleen. We conclude that CsA differentially affects IL-10 production in vivo depending on the nature of the eliciting agent. This observation might be relevant to clinical settings, especially in organ transplantation.
Durez
P
P
Laboratoire Pluridisciplinaire de Recherche Expérimentale Biomédicale, Hôpital Erasme, Brussels, Belgium.
Abramowicz
D
D
Gérard
C
C
Van Mechelen
M
M
Amraoui
Z
Z
Dubois
C
C
Leo
O
O
Velu
T
T
Goldman
M
M
D000818:Animals; D017252:CD3 Complex / Q000502:physiology*; D016572:Cyclosporine / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012333:RNA, Messenger / Q000235:genetics
D017252:CD3 Complex; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016753:Interleukin-10; D016572:Cyclosporine