Apoptosis: a target for potentiation of UV-induced IL-1Ra synthesis by IVIg.
IL-1Ra prevents IL-1 induced inflammatory signalling, a mechanism potentially important for several pathological conditions characterized by inflammation. When administered as a drug in the recombinant form, it displays a protective effect towards them. We postulated that this action could also be achieved by pharmacological activation of endogenous IL-1Ra production. We previously showed that photochemotherapy and UV-light increased monocyte/macrophages IL-1Ra secretion. A similar effect has been shown for IVIg. The aim of this study was to define optimal in vitro conditions for induction of IL-1Ra secretion. As both agents induce lymphocytes apoptosis, we focused our analysis on the influence of IVIg on UV-induced-IL-1Ra production on this mechanism. After overnight preincubation at 37 degrees C, UV-irradiated PBL mixed with two IVIg concentrations (1 and 25 mg/ml) were cocultured with autologous PBMC. Apoptosis was measured by annexin V/PI. IL-1Ra secretion was evaluated by RT-PCR and Luminex microbead array assay. A significant additive dose-dependent influence of IVIg (+85%; p=0.0005) on UV-induced IL-1Ra secretion, involved both Fc-receptor activation at a low dose (1 mg/ml) and a potent apoptotic action on PBL reinforcing the UV effect at high concentrations (25 mg/ml). We conclude that lymphocyte apoptosis represents an important pathway contributing to enhancement of UV-induced monocyte/macrophages IL-1Ra production by IVIg and that these findings should be considered when evaluating in vivo protocols for photochemotherapy and IVIg treatment, in hope of improving efficacy.
Craciun
Ligia I
LI
Department of Immunology, Haematology and Transfusion, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium.
DiGiambattista
Mario
M
Laub
Ruth
R
Goldman
Michel
M
Dupont
Etienne
E
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000378:metabolism*; D066298:In Vitro Techniques; D053590:Interleukin 1 Receptor Antagonist Protein / Q000096:biosynthesis* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014466:Ultraviolet Rays
D016756:Immunoglobulins, Intravenous; D053590:Interleukin 1 Receptor Antagonist Protein