DICHOTOMY BETWEEN THE INNATE IMMUNE RESPONSES BY ALL TRANS- RETINOIC ACID TREATMENT IN A MODEL OF LPS-INDUCED IMMUNOSUPPRESSION

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

Los Cocos

Congreso; LXI Reunión Anual de la Sociedad Argentina de Inmunología; 2013

Sociedad Argentina de Inmunología (SAI)

Immunosuppression (IS) related to late phases of sepsis is a medical concern. The model of tolerance to LPS mimics aspects of sepsis-associated IS, as exposure to repetitive doses of LPS generates a refractory state, where animals inyected with letal dosis of LPS survive and have low amounts of LPS-induced TNF. Despite impaired immune functions in LPS-induced IS, the clearance of bacteria is increased in part due to neutrophils (PMN) activity. All-trans-retinoic acid (ATRA) is a derivative of vitamin-A with immunomodulating properties. Our objective was to study the effects of ATRA on innate an adaptive responses in LPS-induced IS. We used a murine model inyecting increasing e.v. doses of LPS for 20 days simultaneously with oral doses of ATRA (IS group: 5 to 20µg/day/mouse of LPS, IS+ATRA group: LPS+500µg/day/mouse of ATRA). When we studied the adptative immune response, we observed an enhanced primary humoral immune response against a particulated T-dependent antigen measured by hemagglutination in the IS+ATRA group (Titre:IS=2133±426, IS+ATRA=6827±1707, p 0.05). Moreover, using flow cytometry we found that ATRA decreased the percentage (%) of myeloid-derived suppressor cells (Gr-1+ CD11b+, IS=1.7±0.2, IS+ATRA=0.9±0.1, p 0.05) in spleen and increased the % of dendritic cells (CD11c+, IS=1.9±0.1, IS+ATRA=3.4±0.4, p 0.05) in lymph nodes. To evaluate the innate immune response we measured bacterial clearance, inoculating intestinal bacteria i.p. and counting remaining bacteria, PMN migration and TNF production in peritoneal lavages after 3h. We found that ATRA treatment did not modify LPS-induced alterations associated to bacterial clearance (Remaining Bacteria (CFU):Control=145,6±89,7, IS=67,1±23,4*, IS+ATRA=40,2±14,1*;pg/ml TNF:Control=143.0±21.8, IS=3.4±1.3*, IS+ATRA=1.4±0.4*; PMN number (x106): Control=2.0±0.7, IS=3.4±0.5*, IS+ATRA=3.7±1.4*; *p 0.05 vs. Control). ATRAs main effects are directed to modulate the adaptive but not the innate immune responses.