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Systemic and local inflammatory processes have a key, mainly detrimental role in the pathophysiology of ischemic stroke. Currently, little is known about endogenous counterregulatory immune mechanisms. We examined the role of the key immunomodulators [CD4.sup.+][CD25.sup.+] forkhead box P3 [(Foxp3).sup.+] regulatory T lymphocytes ([T.sub.reg] cells), after experimental brain ischemia. Depletion of [T.sub.reg] cells profoundly increased delayed brain damage and deteriorated functional outcome. Absence of [T.sub.reg] cells augmented postischemic activation of resident and invading inflammatory cells including microglia and T cells, the main sources of deleterious cerebral tumor necrosis factor-[alpha] (TNF-[alpha]) and interferon-[gamma] (IFN-[gamma]), respectively. Early antagonization of TNF-[alpha] and delayed neutralization of IFN-[gamma] prevented infarct growth in [T.sub.reg] cell-depleted mice. Intracerebral interleukin-10 (IL-10) substitution abrogated the cytokine overexpression after [T.sub.reg] cell depletion and prevented secondary infarct growth, whereas transfer of IL-10-deficient [T.sub.reg] cells in an adoptive transfer model was ineffective. In conclusion, [T.sub.reg] cells are major cerebroprotective modulators of postischemic inflammatory brain damage targeting multiple inflammatory pathways. IL-10 signaling is essential for their immunomodulatory effect., Stroke is the third leading cause of death and the most frequent cause of permanent disability in adults worldwide (1). Despite considerable advances in the understanding of the pathophysiology of [...]

Interleukin-2 (IL-2) enhances immune stimuli and affects B cell differentiation. The aggressiveness and kinetics of gastrointestinal and hepatic inflammation in the presence or absence of viable bacteria in IL-2-deficient mice were measured. Breeding colonies were maintained under specific pathogen-free and germfree (GF) conditions. Findings showed that older GF IL-2-deficient mice develop mild, focal, subclinical gastrointestinal inflammation in a sterile environment.

Background and aims Inappropriate immune responses contribute to the continuous stimulation of the intestinal immune system in chronic inflammatory bowel disease (IBD). Among several pathogenic factors, a numerical deficiency of regulatory T (Treg) cells has been suggested to lead to an insufficient compensation of chronically activated T lymphocytes. This study was conducted to investigate whether increased apoptosis contributes to Treg cell deficiency in IBD and whether successful treatment with antitumour necrosis factor a (TNFa) is achieved by reducing of Treg cell apoptosis. Methods Apoptosis of CD4+Foxp3+ Treg cells in tissue sections of patients with active IBD was analysed by immunohistochemistry and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labelling) staining.Apoptosis of peripheral blood CD4+CD25+Foxp3+ Treg cells was investigated by flow cytometry and annexin- V staining. In addition, caspase activity and apoptosis were measured in sera of patients with IBD treated with anti- TNFa by a luminometric caspase enzyme assay. Results It is demonstrated that patients with active IBD revealed increased apoptosis of local CD4+Foxp3+ Treg cells in the inflamed mucosa compared with non-inflamed control colon tissue. Moreover, in peripheral blood a reduced frequency and increased apoptosis of Treg cells were found and accompanied by elevated caspase activity in the serum. During anti-TNFa treatment, Treg cell apoptosis declined in close correlation with elevated peripheral Treg cell numbers and a decrease of caspase activation and disease activity. Conclusions These data suggest that increased apoptosis of Treg cells plays a potentially important role in the pathogenesis of IBD and can be reversed by anti-TNFa treatment. Measurement of Treg cell apoptosis and serum caspase activity might therefore represent promising tools for monitoring disease activity and treatment response in patients with IBD. [ABSTRACT FROM AUTHOR]

Abstract: Background: : Both normobaric (NBO) and hyperbaric (HBO) oxygen therapy are protective in transient cerebral ischemia. In contrast, in permanent ischemia models, which reflect the majority of clinical strokes, the effectiveness of NBO is unknown, and the effectiveness of HBO is controversial. The goals of the present study were to compare both oxygen therapies in 2 models of permanent ischemia, to study the effect of time window, and to evaluate the combination of both oxygen therapies.Methods:Distal or proximal permanent occlusion of middle cerebral artery (MCAO) was induced by coagulation or filament, respectively. Mice received air, NBO, a single or repeated HBO (3 ata) treatments. Infarct sizes were quantified at 7 days (coagulation) and 24 h (filament), respectively.Results:Following MCA coagulation, infarct volume was 12.9 ± 1.6 mm3in mice breathing air. When started 45 min or 120 min after MCAO, NBO (10.8 ± 2.2) and significantly more potently HBO (7.8 ± 0.9) reduced infarct size. Repeated HBO treatments had no additional effect (8.3 ± 2.3). HBO also significantly decreased TUNEL cell staining at 24 h. Combination of 60 min NBO plus 60 min HBO resulted in smaller cortical infarcts (8.7 ± 1.5) than 120 min NBO alone (11.1 ± 3.2). In contrast, infarct volumes in filament-induced permanent MCAO did not differ among rodents receiving air (50 ± 24 mm3), NBO (48 ± 16), or HBO (46 ± 21). After filament-induced transient MCAO, however, HBO reduced infarct volume significantly.Conclusions:NBO and more effectively HBO protect the brain against permanent cortical ischemia. In extensive focal ischemia, however, oxygen therapy is only effective in case of early recanalization. [Copyright &y& Elsevier]