Rasmussen's encephalitis: interleukin-10-dependent Tc2 cell polarization may explain its pathophysiology and clinical course.

Little is known about the cellular immune dynamics and pathophysiology of Rasmussen's encephalitis (RE). We investigated transcriptional expression of pro- and anti-inflammatory cytokines and characterized the T-cell subset types present in temporal and frontal lobe specimens obtained from a child with RE. Interleukin (IL)-10 and macrophage scavenger receptor type I mRNA assessed by semiquantitative reverse transcription polymerase chain reaction was found in temporal but not in affected frontal lobe tissue. Messenger RNA specific to tumor necrosis factor alpha, IL-l, IL-4, IL-6, IL-12, IL-15, IL-18, transforming growth factor beta, CD-14, and inducible nitric oxide synthase was not detected in either temporal or frontal tissue with histopathologically manifest evidence of disease. Virtually all lymphocytic infiltrate consisted of CD3+ CD8+ T cells. We speculate that RE is a disease mediated by Tc2 polarization of the immune response and that its immunohistopathology, natural history, and clinical evolution (chronic, staircase progression) reflect the dual/pleiotropic actions of IL-10, which, depending on the state of activation of the immune system, may be either cytolytic or immunosuppressant.

Infection-induced modulation of m1 and m2 phenotypes in circulating monocytes: role in immune monitoring and early prognosis of sepsis.

To monitor and better understand the immunoinflammatory sequelae in sepsis and septic shock, systemic and monocyte-related cytokine responses were evaluated in baboons with experimental peritonitis induced by an E. coli-laden fibrin clot. Despite similar bacterial inocula, considerable interindividual variability in clinical manifestation and outcome of infection was observed. Because monocytes and macrophages are a key component of innate immunity, we hypothesized that early polarization of distinct activation programs in circulating monocytes that culminates in the emergence of either classically (M1) or alternatively (M2) activated monocytes may underlie the observed susceptibility or resistance to infection. To test our hypothesis, we analyzed infection-induced expression of cytokine mRNAs in monocytes isolated from surviving and dead animals. Our data show that resistance to E. coli sepsis may well be associated with a mixed M1/M2 activation state of circulating monocytes, whereas M1 phenotype appeared to be prevailing in monocytes from animals that died. Together with data on systemic cytokine responses, the latter findings indicate that morbidity and mortality of animals with gram-negative sepsis may well result from an overwhelming proinflammatory response. Collectively, our data contribute to a better understanding of cytokine networking in the immunoinflammatory response to microbial infection and suggest M1/M2 immunophenotypic profiling of readily available circulatory monocytes for early prognosis of severe infections.