Current knowledge states that periodontal diseases are chronic inflammatory reactions raised in response to periodontopathogens. Many cell types and mediators, including Th1 and Th2 lymphocytes, cytokines and chemokines, appear to be involved in the immunopathogenesis of periodontal diseases. Chemokines, a family of chemotactic cytokines, bind to specific receptors and selectively attract different cell subsets to the inflammatory site. They can also interact with classical cytokines and modulate the local immune response. In order to study the role of chemokines in periodontal diseases, we examined the expression of chemokines, chemokine receptors and cytokines by means of reverse transcription-polymerase chain reaction (RT-PCR) techniques. Characteristic patterns of such factors' expression were found in gingival biopsies from patients presenting with aggressive periodontitis and chronic periodontitis. The expression of the chemokines macrophage inflammatory protein-1 alpha (MIP-1alpha) and interferon-gamma inducible protein 10 (IP-10) and of their respective receptors, CCR5 and CXCR3, were more prevalent and higher in aggressive periodontitis, and associated with higher interferon-gamma (IFN-gamma) expression and lower interleukin-10 (IL-10) expression. In contrast, chronic periodontitis patients exhibited a more frequent and higher expression of monocyte chemoattractant protein-1 (MCP-1) and its receptor CCR4, and higher expression of IL-10. It is possible that chemokines, in addition to the classical cytokines, are involved in the immunopathogenesis of periodontal disease, driving the migration and the maintenance of several inflammatory cell types such as polymorphonuclear leukocytes, dendritic cells (DCs), natural killer cells, macrophages, and subsets of lymphocytes in the gingival tissues. These cells are thought to participate in the inflammatory and immune reaction that takes place in periodontal disease, killing pathogens, presenting antigens, and producing cytokines. The selective recruitment of polarized lymphocyte subsets could result in differential cytokine production at the site of response, which is supposed to determine the stable or progressive nature of the lesion. Besides, the role of chemokines as activators and chemoattracts of osteclasts may be involved in the determination of disease severity.

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The pathogenesis of myocarditis during Trypanosoma cruzi infection is poorly understood. We investigated the role played by chemokine receptor 5 (CCR5) in the influx of T cells to the cardiac tissue of T. cruzi-infected mice. mRNA and protein for the CCR5 ligands CCL3, CCL4, and CCL5 were detected in the hearts of infected mice in association with CD4+ and CD8+ T cells. There was a high level of CCR5 expression on CD8+ T cells in the hearts of infected mice. Moreover, CCR5 expression on CD8+ T cells was positively modulated by T. cruzi infection. CCR5-deficient mice infected with T. cruzi experienced a dramatically inhibited migration of T cells to the heart and were also more susceptible to infection. These results suggest that CCR5 and its ligands play a central role in the control of T cell influx in T. cruzi-infected mice. Knowledge of the mechanisms that trigger and control the migration of cells to the heart in patients with Chagas disease may help in the design of drugs that prevent myocarditis and protect against the development of severe disease.

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The strong inflammatory reaction that occurs in the heart during the acute phase of Trypanosoma cruzi infection is modulated by cytokines and chemokines produced by leukocytes and cardiomyocytes. Matrix metalloproteinases (MMPs) have recently emerged as modulators of cardiovascular inflammation. In the present study we investigated the role of MMP-2 and MMP-9 in T. cruzi-induced myocarditis, by use of immunohistochemical analysis, gelatin zymography, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction to analyze the cardiac tissues of T. cruzi-infected C57BL/6 mice. Increased transcripts levels, immunoreactivity, and enzymatic activity for MMP-2 and MMP-9 were observed by day 14 after infection. Mice treated with an MMP inhibitor showed significantly decreased heart inflammation, delayed peak in parasitemia, and improved survival rates, compared with the control group. Reduced levels of cardiac tumor necrosis factor-alpha, interferon-gamma, serum nitrite, and serum nitrate were also observed in the treated group. These results suggest an important role for MMPs in the induction of T. cruzi-induced acute myocarditis.