IMEX   05356
INSTITUTO DE MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Increased tumor growth due to attenuation of the immune response by tumor-induced systemic inflammation.
Autor/es:
BRUZZO JUAN, CHIARELLA PAULA, RUGGIERO RAúL A.
Lugar:
Buenos Aires
Reunión:
Congreso; 1º Congreso Franco-Argentino de Inmunología. LVIII Reunión Anual de la Sociedad Argentina de Inmunología.; 2010
Resumen:
Although the link between cancer and local inflammation has firmly been established, the relationship between cancer and systemic inflammation (SI) has comparatively been less studied. We know that the subcutaneous (s.c.) growth of the immunogenic methylchonlanthrene-induced murine fibrosarcoma MCC is accompanied by manifestations of SI when the tumor exceeds 500 mm3 coincidental with the onset of a state of immunosuppression. The aim of this work was: a) to determine if SI was followed by compensatory manifestations of systemic counter-inflammation (SCI); b) to evaluate the influence of SI/SCI on tumor growth; c) to study if the putative influence of SI and/or SCI on tumor growth could be associated with a deleterious effect on the immune system. Results: a) The anti-inflammatory cytokines TGF-â and IL-10 were increased in serum of tumor-bearing mice that exceeded 500 mm3 (p<0.05; p<0.01, respectively). b) When the anti-inflammatory drug indomethacin was inoculated intraperitoneally (i.p.) every 3 days throughout tumor growth, SI was reduced and s.c. tumor growth was retarded as compared with controls (p<0.05). Reciprocally, the i.p. inoculation of the pro-inflamatory thioglicolate (TG) at the time of tumor implant, generated a transient SI accompanied by a faster s.c. tumor growth as compared with controls (p<0.01). c) The i.p. inoculation of TG in immunized non-MCC tumor bearing mice and in mice bearing small MCC tumors, sharply reduced both sinecomitant and concomitant anti-tumor immunity (p<0.01) and this effect was restored by indomethacin. Taken together, our results suggest that MCC tumor growth is enhanced by SI and that this enhancement would be mediated, at least in part, by a deleterious effect on the immune system.