Protective effects of sialylated oligosaccharides in immune complex-induced acute lung injury.

Abstract

SummaryUsing sialyl Lewis x (SLX) oligosaccharides derived from fucosyl transferase-expressing cells or generated synthetically, the ability of these compounds to protect against acute lung damage after deposition of immunoglobulin (Ig)G or IgA immune complexes has been determined. The synthetic compounds were tetra-and pentasaccharide derivates of SLX as well as the nonfucosylated forms of SLX as controls. In the IgG immune complex modal of lung injury, which is E-selectin dependent, SLX preparations provided dose-dependent protective effects, as assessed by changes in lung vascular permeability and hemorrhage. Protective effects were associated with diminished tissue accumulation of neutrophils in lungs (as assessed by myeloperoxidase). Morphological assessment revealed reduced physical contact of neutrophils with the pulmonary vascular endothelium and reduced tissue accumulation of neutrophils. In the model of IgA immune complex-induced lung injury, which does not involve participation of neutrophils and is independent of the requirement for E-selectin, SLX preparations were not protective. These data suggest that, in neutrophil-mediated and E-sdectin-dependent lung injury, SLX preparations provide significant, protective effects against inflammatory vascular injury. The ability to achieve antiinflammatory outcomes in vivo with appropriate oligosaccharides suggests a new approach to the blocking of acute inflammatory responses.

Thoracotomy procedures effect cytokine levels after thoracoabdominal esophagectomy

“…This inflammatory response may play a key role in the development of cell and organ disfunction, which is the basis of ALI and ARDS (6)(7)(8). Cytokines involved in the early phase of inflammatory response include IL1, IL2, IL6 and IL8 (27)(28)(29)(30)(31). Some of these cytokines are produced in the lung by local resident cells such as alveolar macrophages, lung epithelial cells and fibroblasts or by cells such as neutrophils, lymphocytes, monocytes and platelets as a response to local or systemic injury (5,27,(32)(33)(34).…”

Role of interleukin‐4 and interleukin‐10 in murine collagen‐induced arthritis. Protective effect of interleukin‐4 and interleukin‐10 treatment on cartilage destruction

“…Endotoxic shock and cutaneous inflammatory responses were enhanced in IL-10 knockouts (53,54). Likewise, blocking of endogenous IL-10 with neutralizing antibodies enhanced endotoxic shock, IgG immune complex-induced lung injury, and the severity of CIA (27,28,30). The latter study by Kunkel's group showed an increase in IL-10 at the mRNA and protein levels in joint tissues from the onset of arthritis, and accelerated expression of CIA was noted when anti-IL-10 treatment was started on day 24.…”

“…This may provide a reason for uncontrolled cytokine production in RA, and may also offer a therapeutic approach. Efficacy of the in vivo administration of IL-4 or IL-10 has already been shown in TNF/IL-l-dependent animal models, such as endotoxin-induced lethality and IgG immune complexinduced lung injury (27,28), but data in experimental arthritis are scant. Allen et a1 (29) showed that sustained treatment with IL-4 suppressed the chronic, but not the acute, phase of streptococcal cell wall (SCW)-induced arthritis in rats and demonstrated up-regulated IL-1Ra mRNA levels in the monocytes of these animals.…”

IL-10 delivery by AAV5 vector attenuates inflammation in mice with pseudomonas pneumonia

“…[21][22][23][24] IL-10T mice repeatedly exposed to mucoid P. aeruginosa have higher mortality rates and more severe lung pathology when compared with C57BL/6 controls similarly infected; 25 in addition, IL-10T mice have a prolonged inflammatory response to acute P. aeruginosa challenge. 26 Research shows that treatment with IL-10 reduces neutrophil and leukocyte recruitment, decreases proinflammatory cytokine production, and causes an increase in weight loss and tissue injury in the airways of sensitized animals following antigen exposure or P. aeruginosa challenge, 19,21,[27][28][29][30] supporting the use of IL-10 in ameliorating inflammation.…”