Immunobiology
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Cholinesterase inhibitors (Ch-I) improve survival in experimental sepsis consistent with activation of the cholinergic-anti-inflammatory-pathway. So far, less is known about whether Ch-I have a direct immunomodulatory effect on immune cells (polymorphonuclear neutrophils, PMN) in the absence of cholinergic neurons. We investigated the concentration-response-effects of physostigmine and neostigmine on the oxidative burst activity (human and rat PMN) and the expression of adhesion molecules on the surface of human PMN under in vitro conditions. ⋯ While neostigmine has no effect on functional and phenotypic changes of PMN, the lipid soluble Ch-I physostigmine causes a dose dependent reduction in PMA-induced oxidative burst, independent of neuronal released acetylcholine.
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T cells are accumulated in the lungs of chronic obstructive pulmonary disease (COPD) patients. Intraepithelial T cells, expressing the integrin αE (CD103) β7, and regulatory T cells have been implicated in pathogenesis of the disease. We asked whether COPD patients and smokers have altered frequencies of these T cells and if their phenotypes differ. ⋯ Chronic cigarette smoking leads to an accumulation of CD8+ T cells with an altered phenotype in the airway epithelium. The increased frequency of regulatory T cells may influence the ability to regulate smoke-induced inflammation which could be decisive for disease development. Our results further indicate a reversibility of smoke-induced changes.
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The effect of IL-10 antisense oligodeoxynucleotides (ODN) on the susceptibility of burned mice to intradermal (i.d.) infection of methicillin-resistant Staphylococcus aureus (MRSA) was studied. Abscesses formed and sepsis did not develop in normal mice infected i.d. with 10(8)CFU/mouse of MRSA. Similarly, sepsis caused by MRSA i.d. infection did not develop and abscesses formed in burned mice treated with IL-10 antisense ODN. ⋯ However, an abscess did not form, and sepsis caused by MRSA i.d. infection developed in burned mice that were inoculated with M2Mϕ. These results indicate that severely burned mice treated with IL-10 antisense ODN are resistant against i.d. infection with MRSA. M1Mϕ appeared in the infection site tissues of severely burned mice that were treated with IL-10 antisense ODN may play a role on the abscess formation and inhibiting sepsis caused by MRSA i.d. infection.
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It has been postulated that an early systemic inflammatory response syndrome (SIRS) and a subsequent compensatory anti-inflammatory response syndrome (CARS) occur sequentially in sepsis. Co-existence of both is referred to as mixed antagonist response syndrome (MARS). Pro- and anti-inflammatory cytokine production was investigated in patients with postoperative sepsis, a murine peritonitis model and in vitro to further delineate the interaction of hyper- and hypo-inflammation in sepsis. ⋯ Early postoperative sepsis seems to be characterized by a primary MARS. Sepsis severity was positively correlated with a disproportionate elevation of the anti-inflammatory response relative to the pro-inflammatory response, a pattern reminiscent of TLR-driven responses. Detailed characterization of immune responses in sepsis may help to direct standard therapies and to develop effective immunomodulatory strategies.
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Haemolytic uraemic syndrome (HUS) accounts for the most common cause of childhood acute renal failure. Characterized by the classical triad of a microangiopathic haemolytic anaemia, thrombocytopaenia and acute renal failure, HUS occurs as a result of Shiga-toxin producing microbes in 90% of cases. ⋯ With the advent of improved genetic diagnosis, it is likely that certain cases of infection-induced HUS may be attributed to underlying defects in complement components. This review summarises the interplay between complement and infection in the pathogenesis of HUS.