The pattern of production of cytokine mRNAs is markedly altered at the onset of multiple sclerosis

Musette, Philippe; Benveniste, Olivier; Lim, Annick; Béquet, D.; Kourilsky, Philippe; Dormont, Dominique; Gachelin, Gabriel

doi:10.1016/s0923-2494(97)84408-2

Cited by 29 publications

(12 citation statements)

References 16 publications

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“…The IL-10-secreting T cell frequency was lower in MS patients than controls (50). Also, MS patients had less serum IL-10 protein (51), blood cell IL-10 mRNA (52)(53)(54), and blood cell IL-10 protein (55) than controls. Finally, the IL-10 allele with the low expresser promoter polymorphism was more common in MS patients than controls (56,57).…”

Section: Discussionmentioning

confidence: 94%

IL-10 Signaling Is Essential for 1,25-Dihydroxyvitamin D3-Mediated Inhibition of Experimental Autoimmune Encephalomyelitis

Spach¹,

Nashold

Dittel

et al. 2006

The Journal of Immunology

203

158

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Multiple sclerosis (MS) results from an aberrant, neuroantigen-specific, T cell-mediated autoimmune response. Because MS prevalence and severity decrease sharply with increasing sunlight exposure, and sunlight supports vitamin D3 synthesis, we proposed that vitamin D3 and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) may protect against MS. In support of this hypothesis, 1,25-(OH)2D3 strongly inhibited experimental autoimmune encephalomyelitis (EAE). This inhibition required lymphocytes other than the encephalitogenic T cells. In this study, we tested the hypothesis that 1,25-(OH)2D3 might inhibit EAE through the action of IL-10-producing regulatory lymphocytes. We report that vitamin D3 and 1,25-(OH)2D3 strongly inhibited myelin oligodendrocyte peptide (MOG35–55)-induced EAE in C57BL/6 mice, but completely failed to inhibit EAE in mice with a disrupted IL-10 or IL-10R gene. Thus, a functional IL-10-IL-10R pathway was essential for 1,25-(OH)2D3 to inhibit EAE. The 1,25-(OH)2D3 also failed to inhibit EAE in reciprocal, mixed bone marrow chimeras constructed by transferring IL-10-deficient bone marrow into irradiated wild-type mice and vice versa. Thus, 1,25-(OH)2D3 may be enhancing an anti-inflammatory loop involving hemopoietic cell-produced IL-10 acting on brain parenchymal cells and vice versa. If this interpretation is correct, and humans have a similar bidirectional IL-10-dependent loop, then an IL-10-IL-10R pathway defect could abrogate the anti-inflammatory and neuro-protective functions of sunlight and vitamin D3. In this way, a genetic IL-10-IL-10R pathway defect could interact with an environmental risk factor, vitamin D3 insufficiency, to increase MS risk and severity.

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Section: Discussionmentioning

confidence: 94%

IL-10 Signaling Is Essential for 1,25-Dihydroxyvitamin D3-Mediated Inhibition of Experimental Autoimmune Encephalomyelitis

Spach¹,

Nashold

Dittel

et al. 2006

The Journal of Immunology

203

158

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“…2 However, low levels of IL-10 in serum and decreased levels of IL-10 mRNA in PBMC in MS have also been reported. 28,29 One interpretation may be that the numbers of memory cells (detected after antigenic stimulation) are increased in MS, whereas in vivo overall activated cells (observed without antigenic stimulation) are decreased. Thus, the diverging results in cytokine expression studies applying different approaches indicate the importance of selection of methods in cytokine studies.…”

Section: Discussionmentioning

confidence: 99%

Cytokine analysis in multiple sclerosis by competitive RT - PCR: A decreased expression of IL-10 and an increased expression of TNF-α in chronic progression

Huang

Link

et al. 1999

Mult Scler

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Multiple sclerosis (MS) is an inflammatory, demyelinating disease that is specific to the central nervous system. Cytokines are thought to be key mediators of the autoimmune attack against central nervous system myelin in MS. To investigate the involvement of cytokines in MS, the mRNA levels of interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), interleukin-4 (IL-4) and interleukin-10 (IL-10) in peripheral blood mononuclear cells without stimulation in vitro were quantified by a competitive reverse transcription polymerase chain reaction technique. The level of IL-10 specific mRNA was significantly decreased in 47 MS patients compared with 42 healthy controls (P<0.0001). TNF-alpha was significantly increased in MS patients compared with healthy controls (P=0.014), especially in the patients with chronic progressive MS (P=0.0003). Thus we conclude that there are significant in vivo alterations in cytokine gene expression in the periphery in MS.

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“…However, repeated in vitro stimulation of these T cell lines progressively shifts cytokine production toward the Th2 response (9,10). Similarly, repeated COP-I injections may lead to deviation from Th1 to Th2 response in patients with MS (11,12). Studies reported by other investigators, however, indicate that the effect of COP-I on the induction of T cell activation is not entirely selective for Th2 cells and that it consistently activates the production of Th1 and Th2 cytokines in MS (13).…”

Section: Copolymer-i (Cop-i) Has Unique Immune Regulatory Properties mentioning

confidence: 99%

Induction of CD4⁺CD25⁺regulatory T cells by copolymer-I through activation of transcription factor Foxp3

Hong

Zhang

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

257

155

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The pattern of production of cytokine mRNAs is markedly altered at the onset of multiple sclerosis

Cited by 29 publications

References 16 publications

IL-10 Signaling Is Essential for 1,25-Dihydroxyvitamin D3-Mediated Inhibition of Experimental Autoimmune Encephalomyelitis

IL-10 Signaling Is Essential for 1,25-Dihydroxyvitamin D3-Mediated Inhibition of Experimental Autoimmune Encephalomyelitis

Cytokine analysis in multiple sclerosis by competitive RT - PCR: A decreased expression of IL-10 and an increased expression of TNF-α in chronic progression

Induction of CD4⁺CD25⁺regulatory T cells by copolymer-I through activation of transcription factor Foxp3

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The pattern of production of cytokine mRNAs is markedly altered at the onset of multiple sclerosis

Cited by 29 publications

References 16 publications

IL-10 Signaling Is Essential for 1,25-Dihydroxyvitamin D3-Mediated Inhibition of Experimental Autoimmune Encephalomyelitis

IL-10 Signaling Is Essential for 1,25-Dihydroxyvitamin D3-Mediated Inhibition of Experimental Autoimmune Encephalomyelitis

Cytokine analysis in multiple sclerosis by competitive RT - PCR: A decreased expression of IL-10 and an increased expression of TNF-α in chronic progression

Induction of CD4+CD25+regulatory T cells by copolymer-I through activation of transcription factor Foxp3

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Induction of CD4⁺CD25⁺regulatory T cells by copolymer-I through activation of transcription factor Foxp3