Th1/Th2 cytokine patterns and clinical profiles during and after pregnancy in women with multiple sclerosis

Al-Shammri, Suhali; Rawoot, Parvez; Azizieh, Fawaz; AbuQoora, Amr; Hanna, Magdy G.; Saminathan, T.R; Raghupathy, Raj

doi:10.1016/j.jns.2004.03.027

Cited by 94 publications

(65 citation statements)

References 25 publications

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“…These patients showed a considerable shift from a T H 2 profile during pregnancy to a T H 1 cytokine profile postnatal; this was suggestive evidence for the effect of pregnancy in this T H 1-mediated disease (Al-Shammri et al 2004). Building on those findings, the present investigation studied the role of estrogen during EAE.…”

Section: Introductionmentioning

confidence: 65%

Medium-dose estrogen ameliorates experimental autoimmune encephalomyelitis in ovariectomized mice

Haghmorad

Salehipour

Nosratabadi

et al. 2016

Journal of Immunotoxicology

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Estrogen is a neuro-protective hormone in various central nervous system (CNS) disorders. The present study evaluated the role of estrogen during experimental autoimmune encephalomyelitis (EAE) at doses selected to mimic any suppressive potential from the hormone during pregnancy. Here, mice were ovariectomized and then 2 weeks later treated with MOG antigen to induce EAE. Concurrently, mice then received (subcutaneously) an implanted pellet to deliver varying estrogen amounts over a 21-day period. Clinical scores and other parameters were monitored daily for the 21 days. At the end of the period, brain/spinal cord histology was performed to measure lymphocyte infiltration; T-cell profiles were determined through ELISA, flow cytometry, and real-time PCR. Transcription factor expression levels in the CNS were assessed using real-time PCR; T-cell differentiation was evaluated via flow cytometry. The results demonstrated that estrogen inhibited development of EAE. Histological studies revealed limited leukocyte infiltration into the CNS. High and medium dose of estrogen increased T H 2 and T reg cell production of interleukin (IL)-4, IL-10, and transforming growth factor (TGF)-b, but concurrently resulted in a significant reduction in production of interferon (IFN)-c, IL-17, and IL-6. Flow cytometry revealed there were also significant decreases in the percentages of T H 1 and T H 17 cells, as well as significant increase in percentages of T reg and T H 2 cells in the spleen and lymph nodes. Real-time PCR results indicated that high-and medium-dose estrogen treatments reduced T-bet and ROR-ct factor expression, but enhanced Foxp3 and GATA3 expression. Collectively, these results demonstrated that a medium dose of estrogen -similar to a pregnancy level of estrogen -could potentially reduce the incidence and severity of autoimmune EAE and possibly other autoimmune pathologies.ARTICLE HISTORY

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Section: Introductionmentioning

confidence: 65%

Medium-dose estrogen ameliorates experimental autoimmune encephalomyelitis in ovariectomized mice

Haghmorad

Salehipour

Nosratabadi

et al. 2016

Journal of Immunotoxicology

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“…Estrogen is thought to exert a biphasic dose effect-lower levels enhance while high levels inhibit specific immune activities whereas progesterone promotes the development of Th2 cells which inhibits the proliferation of the Th1 cells (Whitacre et al, 1999). Pregnancy is associated with a marked increase of estrogen, progesterone and cortisol in the plasma and brings about remission in autoimmune disorders such as RA and multiple sclerosis which are both driven by Th1 cytokines (Al-Shammri et al, 2004;Elenkov et al, 1997). This has been well studied in animal models where progression of pregnancy induces a decline of Th1 cytokines such as IL-2 and interferon gamma while causing a surge in Th2 cytokines, in particular, IL-4 (Elenkov et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in the interleukin-4 and IL-4 receptor genes modify risk for chronic inflammatory arthropathies in women

Suppiah

Rooney

Vandenbroeck

2006

Experimental and Molecular Pathology

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Polymorphisms in the interleukin-4 and IL-4 receptor genes modify risk for chronic inflammatory arthropathies in women. Suppiah, V., Rooney, M., & Vandenbroeck, K. (2006). Polymorphisms in the interleukin-4 and IL-4 receptor genes modify risk for chronic inflammatory arthropathies in women. AbstractRheumatoid and juvenile idiopathic arthritis (RA, JIA) are chronic inflammatory arthropathies with polygenic autoimmune background. We analysed the IL-4 +33 C/T and IL-4R Q551R single nucleotide polymorphisms (SNPs) in 294 RA, 72 JIA and 165 controls from Northern Ireland. Analysis of the individual phenotypes (RA or JIA) showed that both the IL-4 +33 TT (P = 0.02; OR: 0.25, 95% CI: 0.07-0.87) and the IL-4R Q551R CC genotypes (P = 0.001; OR: 0.19, 95% CI: 0.06-0.56) were exclusively decreased in female RA patients compared to female controls. Similar non-significant trends were observed in female JIA patients (OR: 0.25, 95% CI: 0.03-2.11 and OR: 0.31, 95% CI: 0.07-1.47, respectively). Analysis of the common phenotype (inflammatory arthropathy; i.e. JIA and RA combined) corroborated the unique association of these polymorphisms with female inflammatory arthropathy (P = 0.013 and 0.002, respectively). This is the first demonstration of sex-specific association of the two foremost genes of the IL-4 signalling cascade with chronic inflammatory arthropathies.

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“…In addition, estrogen effect on immune function might be biphasic: specifically, low doses of estrogens promote Th1 responses and increase cell-mediated immunity, while high doses result in increased Th-2 responses ( [28,129]). Accordingly, women are more likely to develop a Th1 response to infective agents than men, so they are more susceptible to autoimmune diseases, except during pregnancy where women exhibit a pronounced Th2 response ( [5,183,250]). …”

Section: Estrogens and Multiple Sclerosismentioning

confidence: 99%

Estrogen anti-inflammatory activity in brain: A therapeutic opportunity for menopause and neurodegenerative diseases

Vegeto

Benedusi

Maggi

2008

Frontiers in Neuroendocrinology

278

206

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a b s t r a c tRecent studies highlight the prominent role played by estrogens in protecting the central nervous system (CNS) against the noxious consequences of a chronic inflammatory reaction. The neurodegenerative process of several CNS diseases, including Multiple Sclerosis, Alzheimer's and Parkinson's Diseases, is associated with the activation of microglia cells, which drive the resident inflammatory response. Chronically stimulated during neurodegeneration, microglia cells are thought to provide detrimental effects on surrounding neurons. The inhibitory activity of estrogens on neuroinflammation and specifically on microglia might thus be considered as a beneficial therapeutic opportunity for delaying the onset or progression of neurodegenerative diseases; in addition, understanding the peculiar activity of this female hormone on inflammatory signalling pathways will possibly lead to the development of selected anti-inflammatory molecules. This review summarises the evidence for the involvement of microglia in neuroinflammation and the anti-inflammatory activity played by estrogens specifically in microglia.

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Th1/Th2 cytokine patterns and clinical profiles during and after pregnancy in women with multiple sclerosis

Cited by 94 publications

References 25 publications

Medium-dose estrogen ameliorates experimental autoimmune encephalomyelitis in ovariectomized mice

Medium-dose estrogen ameliorates experimental autoimmune encephalomyelitis in ovariectomized mice

Polymorphisms in the interleukin-4 and IL-4 receptor genes modify risk for chronic inflammatory arthropathies in women

Estrogen anti-inflammatory activity in brain: A therapeutic opportunity for menopause and neurodegenerative diseases

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