Short treatment with the TNF-alpha; blocker infliximab diminishes chronic chagasic myocarditis in rats without evidence of Trypanosoma cruzi reactivation.

PÉREZ AR., FONTANELLA GH, NOCITO AL, REVELLI S, BOTTASSO O.

CLINICAL AND EXPERIMENTAL IMMUNOLOGY

Blackell

Lugar: Pais: Reino Unido; Año: 2009 vol. 157 p. 291 - 299

0009-9104

<!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman";} @page Section1 {size:595.3pt 841.9pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:35.4pt; mso-footer-margin:35.4pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> ABSTRACT   Tumour necrosis factor alpha (TNF-alpha) is crucial for the resistance to Trypanosoma cruzi (T. cruzi) acute infection, but there is scarce information on its role during the chronic phase. To address this issue, we analysed whether a short treatment with a TNF-alpha blocker affected the course and characteristics of chronic disease in a rat experimental model of T. cruzi infection. Anti-TNF-alpha agent (infliximab) was administered during the chronic phase for a period of four weeks (3 mg/kg/week), while control infected rats were inoculated with saline physiologic solution. Search for parasites yielded non-successful results in all infected groups, irrespective of treatment. Nevertheless, presence of T. cruzi kDNA in heart tissue was detected in infected and infected plus treated animals. Since infliximab might induce changes in anti-parasite cytokine response, circulating levels of interleukin (IL)-10, interferon gamma and nitric oxide were evaluated. Only an increase in IL-10 levels was observed in the infected group treated with the anti-TNF-alpha blocker respect the remaining groups (p<0.05). A clear attenuation of histological damage associated with a diminution of cardiac TNF-alpha mRNA expression was observed in the infected and treated animals respect the infected and non-treated group. Blocking of TNF-alpha during a relatively short period in chronically infected rats did not lead to evident parasite reactivation but significantly reduced myocarditis severity, indicating a role of this cytokine in the pathogenesis of chronic myocardial damage.