Exposición a ceniza volcánica producida por el volcán Turrialba y enfermedades respiratorias, Costa Rica, 2016 / Exposure to volcanic ash produced by the Turrialba volcano and respiratory diseases, Costa Rica, 2016

Resumen Objetivo: Describir el comportamiento espacial de la contaminación por cenizas volcánicas y el efecto sobre la incidencia de enfermedades respiratorias agudas y crónicas, en las comunidades expuestas a la ceniza producida por la actividad del Volcán Turrialba, durante el año 2016. Materiales y métodos: Se realizó un estudio ecológico, observacional retrospectivo, transversal y correlacional, en donde se categorizaron 36 cantones a 50 km a la redonda del volcán Turrialba, según su nivel de contaminación. Resultados: Se constata un comportamiento diferenciado en el espacio geográfico de afectación de la pluma de ceniza volcánica, todos los territorios incluidos en el estudio resultaron con algún nivel de contaminación, sin embargo, se distinguen tres zonas, alta, media y baja contaminación. Un 46.6% de los eventos epidemiológicos estudiados poseen un mayor riesgo de presentarse en cantones con alta contaminación, sobre los cantones con media y baja contaminación. Conclusiones: Es posible que la afectación por contaminación debido a la ceniza volcánica haya incrementado el riesgo de exacerbación de enfermedades respiratorias crónicas, en la zona bajo la influencia directa de la pluma de cenizas volcánicas.

Abstract Objective: Describe the spatial behavior of contamination by volcanic ash and the effect on the incidence of acute and chronic respiratory diseases in communities exposed to the ash produced by the activity of the Turrialba Volcano during the year 2016. Materials and methods: An ecological, observational, retrospective, cross-sectional and correlational study was carried out, where 36 cantons within 50 km of the Turrialba volcano were categorized, according to their level of contamination. Results: A differentiated behavior is verified in the geographical space affected by the volcanic ash plume, all the territories included in the study resulted in some level of contamination, however three zones are distinguished, high, medium and low contamination. 46.6% of the epidemiological events studied have a higher risk of occurring in cantons with high contamination, over cantons with medium and low contamination. Conclusions: It is possible that the contamination due to volcanic ash has increased the risk of exacerbation of chronic respiratory diseases in the area under the direct influence of the volcanic ash plume.

Short-term intratumoral interleukin-12 expressed from an alphaviral vector is sufficient to induce an efficient antitumoral response against spontaneous hepatocellular carcinomas.

Interleukin-12 (IL-12) is an immunostimulatory cytokine that has shown strong antitumor effects in animal models of liver cancer. In order to overcome the severe toxicity associated with its systemic administration, we had previously tested different strategies based on IL-12 gene transfer to tumor cells or to the surrounding liver tissue. We obtained promising results both with a recombinant Semliki Forest virus (SFV) vector expressing high levels of IL-12 (SFV-IL-12) after intratumoral injection and with a plasmid vector [pTonL2(T)-mIL12] that allows liver-specific and inducible IL-12 expression. The aim of the present study was to compare the antitumor responses induced by both systems in a clinically relevant animal model of hepatocellular carcinoma (HCC) developed in L-PK/c-myc transgenic mice. These animals overexpress the c-myc oncogene in their livers, giving rise to spontaneous hepatic tumors with latency, histopathology, and genetic characteristics similar to human HCCs. We observed that intratumoral inoculation of SFV-IL-12 induced growth arrest in most tumors, providing 100% survival rate, in contrast to no survival in control animals. Similar results were obtained with hydrodynamic injection of pTonL2(T)-mIL12 after long-term induction of IL-12 expression in the liver. However, tumor arrest was less evident in plasmid-treated mice and the survival rate was slightly lower, despite higher and more sustained levels of IL-12 and IFN-γ in serum. The fact that SFV-IL-12 was able to induce both apoptosis and a type-I IFN response specifically in the tumor could explain why short-term IL-12 expression from this vector was sufficient to mediate an antitumoral response comparable with long-term IL-12 expression driven by pTonL2(T)-mIL12. Since SFV-IL-12 could reduce the possible toxicity associated with long-term IL-12 expression, we believe that this vector could have a potential application for HCC gene therapy.

Induction of immunosuppressive molecules and regulatory T cells counteracts the antitumor effect of interleukin-12-based gene therapy in a transgenic mouse model of liver cancer.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) often lacks curative treatment; therefore new efficient therapies are needed. In this work we aimed at evaluating the antitumor effect of interleukin-12 (IL-12)-based gene therapy on HCC occurring spontaneously in mice. METHODS: A plasmid-vector expressing IL-12 in a liver-specific and doxycycline (Dox)-inducible manner was transferred by hydrodynamic injection to the liver of L-PK/c-myc mice with HCC. IL-12 expression was induced by administering Dox (3 cycles of 1 month duration separated by 1 month rest). RESULTS: Dox administration increased serum IL-12 and IFN-gamma and induced tumor lymphocytic infiltration in all treated mice which was accompanied by tumor stabilization or regression in 40% of animals. The antitumor effect did not correlate with levels of IL-12 or IFN-gamma nor with the intensity of tumor mononuclear infiltration. However, tumors from non-responder mice showed more abundance of Foxp3+ regulatory T cells and higher expression of the immunosuppressive molecules PD-1, PD-L1, VEGF, CTLA-4, IDO, and IL-10 than those that responded to therapy. CONCLUSIONS: Although long-term induction of IL-12 expression in the liver can inhibit HCC growth, the efficacy of the treatment appears to be limited by the activation of immunosuppressive mechanisms.