Is the modulatory effect of pregnancy in multiple sclerosis associated with changes in blood apoptotic molecules?

OBJECTIVE: We examined whether the modulatory effect of pregnancy on multiple sclerosis (MS) is associated with changes in the apoptotic molecules in sera. SUBJECTS AND METHODS: The serum levels of tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL), sFas, Fas ligand (sFasL) and macrophage migration inhibitory factor were analyzed from 19 MS patients and 14 controls during late pregnancy and post-partum. The obtained results were related to disease activity and the progression of MS. RESULTS: Disease activity decreased during pregnancy. The levels of sTRAIL and sFasL increased from late pregnancy to post-partum situation in both MS patients and controls, but in MS patients the changes in the levels of sTRAIL from late pregnancy to post-partum were smaller than in controls. CONCLUSIONS: Post-partum upregulation of TRAIL and FasL seems to be caused by physiologic reactivation of the mother's immune system after pregnancy. An increased risk of relapses in MS post-partum may be associated with changes in the immunomodulatory potential of these apoptotic molecules.

Immunoregulatory factors in multiple sclerosis patients during and after pregnancy: relevance of natural killer cells.

Multiple sclerosis (MS) ameliorates typically during pregnancy but after the delivery the relapse rate often increases. Our study was conducted to understand the immunoregulatory mechanisms accompanying this phenomenon. MS patients were followed-up prospectively during pregnancy and 6 months postpartum, with immunological characterization of the peripheral blood. Groups of age- and parity-matched healthy pregnant women, and age- and sex-matched non-pregnant women and non-pregnant MS patients were studied as controls. In our patient cohort, the annualized relapse rate was 1.0 +/- 1.0 relapses/woman/year (mean +/- standard deviation) during the year before pregnancy, but dropped to 0.2 +/- 0.9 during the third trimester (P = 0.02). After the delivery the relapse rate increased again to 1.4 +/- 1.9 (1-3 months postpartum versus third trimester P = 0.003). While percentages of peripheral blood CD3, CD4, CD8 and CD19 immune cell subsets were unchanged over the observation period, reduced disease activity during the last trimester was associated with a significant increase in the percentage of circulating CD56(bright) natural killer (NK) cells. Simultaneously, the proportion of circulating CD56(dim) NK cells was clearly reduced. No alteration was noted in CD4+ CD25(high) forkhead box P3+ regulatory T cells. Production of interferon-gamma by peripheral blood lymphocytes was down-regulated significantly during pregnancy in comparison to the postpartum period, resulting in an increased T helper type 2 (Th2) : Th1 ratio during pregnancy. In conclusion, pregnant state in MS patients is characterized by an increase in the percentage of CD56(bright) NK cells and by enhanced Th2 type cytokine secretion. Our findings suggest a potential role for CD56(bright) regulatory NK cells in the control of autoimmune inflammation during pregnancy in MS.

Interleukin-6, interleukin-1 receptor antagonist and interleukin-1beta production in patients with focal epilepsy: A video-EEG study.

UNLABELLED: Experimental and clinical studies have shown that prolonged seizures result in increased cytokine production in the central nervous system. The purpose of this study was to examine plasma concentrations of interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1Ra), and interleukin-1 beta (IL-1beta) in 20 patients with epilepsy undergoing a video-EEG study. Plasma samples were obtained at the onset of the recordings and 3, 6, 12 and 24 h after the index seizure. Localization of the seizure focus and classification of epilepsy was based on concordant electroclinical findings in the video-EEG study, and on MRI examination. Patients were divided into two groups: temporal lobe epilepsy (TLE) (n=11), and extratemporal lobe epilepsy (XLE) (n=9). RESULTS: Only the TLE group showed significant increase in plasma levels of IL-6 peaking at 6 h postictally. Postictal plasma levels of IL-1RA and IL-1beta did not significantly differ from baseline levels in either of the patient groups. IL-1RA showed a decreasing trend (p>0.059) in TLE patients during 12 to 24 postictal hours. CONCLUSIONS: This study further supports the role of focal seizures in regulation of cytokine responses.