MODULATION OF SYSTEMIC IMMUNITY BY ALLTRANS RETINOIC ACID ADMINISTRATION (ATRA) IN A MURINE MODEL OF LIPOPOLYSACCHARIDE-INDUCED IMMUNOSUPPRESSION

MARTIRE GRECO D; RODRIGUEZ-RODRIGUES N; LANDONI V; MEISS R; CHIARELLA P; REARTE B; SCHIERLOH P; ISTURIZ MA; FERNÁNDEZ GC

Mar del Plata

Congreso; LXII Reunión Anual de la Sociedad Argentina de Inmunología; 2014

Sociedad Argentina de Inmunología (SAI)

Efforts to recover the immune functions of patients with postsepsis immunosuppression will be a breakthrough in the management of this condition. All-trans retinoic acid (ATRA) is a derivative of vitamin A with immunomodulatory properties that have effects on different immune cell populations. Our aim was to study different effects of ATRA on the systemic immune response in immunosuppressed mice (IS) by chronic inoculation of LPS and concomitant ATRA administration. For this purpose we apply daily increasing doses of LPS i.p. (5-100 μg/day/mouse) for 20 days and administered ATRA orally or i.p. (500 μg/day/mouse) (IS+ATRA group) or vaseline (vehicle) (IS group). Oral administration of ATRA to IS mice was able to increase the removal of bacteria in the peritoneal cavity after 3 h of bacterial inoculation (remaining colony formation units in peritoneal lavages: IS = 82±13, IS+ATRA = 38±9, p 0.05), but did not alter the number of splenic leucocytes (Total leukocyte number (x107) IS = 3.9±0.3, IS+ATRA = 3.7±0.6) or T cell proliferation in vitro using Concanavalin A and revealed by the MTT technique (O.D. 570 nm: IS = 0.51±0.07, IS+ATRA = 0.62±0.05). However, when ATRA was administered to IS mice i.p., proliferation of T cells in the spleen was restored, and this was associated with a decreased number of Myeloid derived Suppressor cells (MDSC) and a partial recovery in the histological organization of the spleen (O.D. 570 nm: IS = 0.22±0.04, IS+ATRA = 0.75±0.05; Number of MDSC (x107): IS = 2.8±0.4, IS+ATRA = 1.2±0.1, p 0.05). Our results indicate that ATRA is able to restore the innate immune response and that the selective effects of ATRA in the spleen depend on the route of administration.