Application thérapeutique de l'IL-4 dans un modèle de souris irradiées corps entier à dose létale
Radioprotection 37 (4), 411-426, 2002 (in French)
A. Van Der Meeren, L. Lebaron-Jacobs, M.-H. Gaugler, M.-A. Mouthon, P.
Monti, C. Marquette and P. Gourmelon
In the present study, we determined the consequences of IL-4 treatment on survival, hematopoietic recovery as well as acute inflammatory response of irradiated mice. Mice were total body irradiated with lethal doses of -rays and treated with IL-4 30 min or 2 h after exposure. Our data show an enhancement of the 30-day survival after 8 Gy irradiation, from 20% for placebo-treated mice to 75% with IL-4. It is generally admitted that the death of animals occurring in this dose range is due to hematopoietic syndrome. Therefore, we determined the efficacy of IL-4 on promoting the recovery of blood cell counts and progenitors in bone marrow. The hematopoietic status of animals is the same whether or not treated with IL-4. Given the anti-inflammatory properties of IL-4, we studied the consequences of IL-4 treatment on the inflammatory response within 24 h after 8 Gy exposure. We have shown that IL-4 treatment led to a limitation of the release of inflammatory mediators, such as IL-1 or KC, in the plasma or tissues of irradiated mice. On the other hand, IL-4 improved the
radio-induced metabolic and functional damages in the central nervous system. In conclusion, our results have shown an enhanced survival of IL-4 treated irradiated mice without improvement of hematopoietic reconstitution. Therapeutic potential of IL-4 could result, at least in part, from the limitation of the radio-induced inflammatory response.