Cytokine mRNA levels in mononuclear blood cells from patients with multiple sclerosis

Rieckmann, Peter; Albrecht, M.; Kitze, Bernd; Weber, Thomas K.; Tumani, Hayrettin; Broocks, Andreas; Lüer, W.; Poser, S.

doi:10.1212/wnl.44.8.1523

Cited by 220 publications

(88 citation statements)

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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: 93%

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: 93%

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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“…In experimental African trypanosomiasis, immune dysfunction is associated with abnormal cytokine response [5]. Other studies have documented that the IFN-␥ mRNA expression is correlated closely with the protein production [24,25]. IFN-␥ can be stimulated by both intracellular [26] and extracellular parasites [4], and has been considered as an important element in the host parasite interactions.…”

Section: Discussionmentioning

confidence: 99%

Interferon‐γ and Interleukin‐12 Genes are Preferentially Expressed During Early Experimental African Trypanosomiasis and Suppressed by Denervation of the Spleen

Liu

Ragaa

et al. 1999

Scand J Immunol

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The cross talk between the central nervous system (CNS) and the immune system includes among others, the modulation of immune responses by the autonomic nervous system. Here, we investigated the effects of a splenic denervation on cytokine induction in early experimental African trypanosomiasis. Profiles of the cytokine mRNA expression for interleukin (IL)‐4, interleukin (IL)‐6, interleukin (IL)‐10, interleukin (IL)‐12, tumour necrosis factor (TNF)‐α, tumour necrosis factor (TNF)‐β, transforming growth factor (TGF)‐β and interferon (IFN)‐γ were examined at 4 h, 8 h and 12 h postinfection (p.i.), and in noninfected controls. Only IFN‐γ and IL‐12 were significantly expressed over noninfected controls. Already at 4 h p.i. both cytokines were expressed and showed more increased levels at 12 h. Sympathetic denervation of the spleen markedly reduced the mRNA expression for both IFN‐γ and IL‐12. Con A was used as a positive control and showed an enhanced mRNA expression, which was also suppressed by a splenic denervation. To demonstrate that the mRNA expression had resulted in a cytokine production, we looked for the protein level of IFN‐γ at 4 h p.i. by immunohistochemistry and found increased levels of IFN‐γ, which was also inhibited by the denervation. Sham‐operated animals exhibited similar responses as the nondenervated controls. Our data present for the first time very early kinetics for a cytokine gene expression during an experimental African trypanosomiasis. Furthermore, the data suggest a regulatory role for the autonomic nervous system on cytokine responses at both the mRNA and the protein levels.

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“…The main aim was to show basic applicability of RT mRNA measurements of cytokine response in an in vitro stimulation test. The method has been mainly applied presently in tissue biopsies [15] and in studies of in vivo activated cells [16]. …”

Section: Discussionmentioning

confidence: 99%

Interferon‐γ Production in Antigen Specific T Cell Response: Quantitation of Specific mRNA and Secreted Protein

et al. 1997

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Halminen M, Klemetti P, Vaarala O, Hurme M, Ilonen J. Interferon-g Production in Antigen Specific T Cell Response: Quantitation of Specific mRNA and Secreted Protein. Scand J Immunol 1997;46:388-392 Interferon gamma (IFN-g) production as a measure of cellular sensitization was studied by detection of the cytokine in culture supernatant by enzyme immunoassay (EIA) and by measuring cellular mRNA using the reverse transcriptase polymerase chain reaction (RT-PCR) method. These assays were compared to the standard lymphocyte proliferation assay as a marker of T cell responsiveness to foreign antigens. When blood donors seropositive for herpes simplex virus (HSV) were compared to seronegative donors, all measurements of cellular sensitization separated the groups without overlap. There were significant correlations between the IFN-g mRNA titre and the secreted IFN-g (r ¼ 0.57, P ¼ 0.03), and the proliferative response and the secreted IFN-g (r ¼ 0.78, P ¼ 0.001), as well as between the IFN-g mRNA titre and the proliferative response (r ¼ 0.78, P < 0.001). When tetanus toxoid (TT) responses were studied in immunized subjects, a wide range of responsiveness could be seen and correlation between various measurements was poor. However, constant individual levels of the cytokine production were demonstrated. Six people who had received their last TT booster vaccination more than 5 years ago were revaccinated and repeatedly studied. An increase in the levels of produced IFN-g could be seen in all subjects and two who lacked a lymphocyte proliferation response developed it after revaccination.

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Cytokine mRNA levels in mononuclear blood cells from patients with multiple sclerosis

Cited by 220 publications

References 0 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

Interferon‐γ and Interleukin‐12 Genes are Preferentially Expressed During Early Experimental African Trypanosomiasis and Suppressed by Denervation of the Spleen

Interferon‐γ Production in Antigen Specific T Cell Response: Quantitation of Specific mRNA and Secreted Protein

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