TNFalpha and IL-1beta effects on thymus apoptosis duringTrypanosoma cruzi during acute infection in C57BL/6

PÉREZ AR, NICORA A, PALAZZI J, BESEDOVSKY H, DEL REY A, ROGGERO E, BOTTASSO O.

Rosario, Argentina

Otro; XX Annual Meeting of the Argentine Society of Protozoology, May 26-28, 2004; 2004

Sociedad Argentina de Protozoología

Biocell Vol 28 Nº3 – 2004 XX Annual Meeting of the Argentine Society of Protozoology, May 26-28, 2004 TNFa AND IL-1b EFFECTS ON THYMUS APOPTOSIS DURING Trypanosoma cruzi ACUTE INFECTION IN C57BL/6 MICE TNFa AND IL-1b EFFECTS ON THYMUS APOPTOSIS DURING Trypanosoma cruzi ACUTE INFECTION IN C57BL/6 MICE Pérez AR1, Nicora A2, Palazzi J2, Besedovsky H3, del Rey A3, Roggero E1, Bottasso O1. 1Inst. de Inmunología, Fac. Cs. Médicas UNR. 2Inst. de Estudios Bioquímicos (IDEB), Rosario. 3Inst. de Fisiología Normal y Patológica, Universidad Philipps, Alemania. E-mail: bottasso@uolsinectis.com.ar Severity of experimental Trypanosoma cruzi (Tc) acute infection in C57BL/6 (B6) mice is associated with increased serum levels of TNFa, IL-1b and thymic atrophy. Though both cytokines are related with apoptosis induction in thymocytes, we proposed to study whether in deficient receptor mice for both pro-inflammatory cytokines (TNF-R1+2 (-/-) and IL-1R (-/-) could have some modification in the thymic atrophy accompanying such an infection. In view that both cytokines plus IL-6, can increase plasma corticosterone levels (CT) which is able by itself to induce thymocyte apoptosis, we analysed circulating levels of the four mediators in Tc-infected B6 and KO mice. Results (mean ± sem, n=4-5) at day 15 pi: Parasitemia (parasites/50 fields) B6 195±10, TNF-R1+2(-/-) 951±129 (p<0.014 vs B6), IL-1R (-/-) 212±9; TNFa(pg/ml) B6 588±98, TNF-R1+2(-/-) 2990±328 (p<0.014 vs B6), IL-1R(-/-) 579±96; IL-1b(pg/ml) B6 82±13, TNF-R1+2 (-/-) 724±320 (vs B6 p<0,014), IL-1R(-/-) 709±75 (vs B6 p<0,014); IL-6 (pg/ml) B6 527±74, TNFR1+2 (-/-) 1666±588 (vs B6 p<0,014) IL-1R(-/-) 899±172 (vs B6 p<0,029); CT (ug/dl, relative increase day15/day0 pi) B6 3,06±0.2, TNF-R1+2 (-/-) 18.5±6.6 (vs B6 p<0,01), IL-1R(-/-) 5.8±3.8; Apoptosis (relative increase day15/day0 pi) B6 2.8±0.7, TNF-R1+2(-/-) 5.3.0±1.0 (p<0.05 vs B6), IL-1R(-/-) 3.45±0.2. Acute infection in TNF-R1+2 (-/-) mice was associated with a significant increase in CT plasma levels and thymus apoptosis, whereas infection parameters in IL-1R(-/-) mice were similar to those observed in B6 mice. The remarkable increase of thymocyte apoptosis in absence of TNFa signal, could be due to an excessive HPA activation mediated by IL-1b and IL-6. These results extend the redundant effects of these pro-inflammatory cytokines in activating HPA axis within the setting of acute Tc infection.