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Biomedical subjects

Wendy Gilmore

Publications and source records attributed to Wendy Gilmore.

4 recordsLinked to original sources

The risk of relapses in multiple sclerosis during systemic infections.

OBJECTIVES: To assess the risk of multiple sclerosis (MS) relapses, MRI activity, and T cell responses during systemic infections (SI) in patients with MS. METHODS: The authors prospectively studied 60 patients with MS. Twenty patients were evaluated with sequential MRI on initial visit, and 2 and 12 weeks later. Blood samples were collected at first infection symptom and 2, 5, 12, and 24 weeks later, and production of IL-4, IL-10, IL-12, IFN-gamma, TNFalpha, VLA-4, LFA-1, MMP-9, and MMP-2 were measured after infectious antigens (Ag) stimulation. RESULTS: Increased risk of relapse and MRI activity were observed during SI. Numbers of IFN-gamma, TNFalpha, and IL-12 secreting cells, serum concentrations of MMP-9, and expression of VLA-4 and LFA-1 after PBMC viral or bacterial Ag stimulation were higher in samples collected during exacerbations associated to SI. Transwell analysis demonstrated that soluble factors produced during viral stimulation have little effect on myelin specific T cells activity. In contrast, PBMC viral stimulation in the presence of cognate myelin Ag induces maximal effector responses at 20 to 30 times lower than the Ag alone. CONCLUSIONS: There was a significant association between systemic infections and risk of MS relapse, increased MRI activity, and T cells activation. Furthermore, infectious agents increased myelin specific T-cells sensitivity to cognate Ag.

Adult↗

A live diarrheal vaccine imprints a Th2 cell bias and acts as an anti-inflammatory vaccine.

An experimental vaccine for enterotoxigenic Escherichia coli (ETEC) composed of a live, attenuated Salmonella vector-expressing enterotoxigenic E. coli fimbriae, colonization factor Ag I (CFA/I), stimulated a biphasic Th cell response when given orally and suppressed the normally produced proinflammatory response. Such suppression was also evident upon the Salmonella-CFA/I infection of macrophages resulting in diminished TNF-alpha, IL-1, and IL-6 production and suggesting that the CFA/I fimbrial expression by Salmonella may protect against a proinflammatory disease. To test this hypothesis, SJL/J mice were vaccinated with Salmonella-CFA/I construct 1 or 4 wk before induction of experimental autoimmune encephalomyelitis using an encephalitogenic proteolipid protein peptide, PLP(139-151). Mice receiving Salmonella-CFA/I vaccine recovered completely from mild acute clinical disease and showed only mild inflammatory infiltrates in the spinal cord white and gray matter. This protective effect was accompanied by a loss of encephalitogenic IFN-gamma-secreting Th cells and was replaced with an increase in IL-4, IL-10, and IL-13 secretion. Collectively, these data suggested that Salmonella-CFA/I is an anti-inflammatory vaccine that down-regulates proinflammatory cells and confers protection against a proinflammatory disease, experimental autoimmune encephalomyelitis, via immune deviation.

Administration, Oral↗

Preliminary studies of cytokine secretion patterns associated with pregnancy in MS patients.

Multiple sclerosis has a tendency to remit during pregnancy, followed by an increase in the risk for disease relapses in the postpartum period. In this communication, preliminary data are presented to indicate that activated peripheral blood mononuclear cells (PBMC) from the postpartum period secrete elevated levels of gamma-interferon (IFN-gamma) relative to those collected during the third trimester. In addition, myelin antigen-specific T cell lines established from the third trimester of pregnancy secrete elevated levels of interleukin-10. The data suggest that the study of the mechanisms underlying natural fluctuations in disease activity during pregnancy and the postpartum period holds promise for a better understanding of factors capable of initiating and regulating remission and exacerbation in MS.

Adult↗

Increased CXCL8 (IL-8) expression in Multiple Sclerosis.

Multiple Sclerosis (MS) is a chronic inflammatory disease of the CNS which is characterized by large mononuclear cell infiltration and significant demyelination. CXCL8 is a chemo-attractant for both neutrophils and monocytes and triggers their firm adhesion to endothelium. In this study, we demonstrate that serum CXCL8 and CXCL8 secretion from PBMCs are significantly higher in untreated MS patients compared to controls and are significantly reduced in MS patients receiving interferon-beta1a therapy. We suggest that CXCL8 may serve as a marker of monocyte activity in MS and may play a role in monocyte recruitment to the CNS.

Adult↗