Apoptosis: A target for potentiation of UV-induced IL-1RA synthesis by IVIg

作者:Craciun Ligia I; DiGiambattista Mario; Laub Ruth; Goldman Michel; Dupont Etienne*
来源:Immunology Letters, 2007, 110(1): 36-41.
DOI:10.1016/j.imlet.2007.02.010

摘要

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-1 Ra 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 (I 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.