Use of the dexamethasone-corticotrophin releasing hormone test to assess hypothalamic-pituitary-adrenal axis function in rheumatoid arthritis.

Objectives. Hypothalamic-Pituitary-Adrenal axis function may be abnormal in rheumatoid arthritis (RA). A pilot study in 7 patients suggested impaired glucocorticoid feedback in some patients after the dexamethasone-corticotrophin releasing hormone (CRH) test. This study aimed to investigate the dexamethasone-corticotrophin releasing factor test in a larger group of patients and relate the results to characteristics of the disease. Methods. Outpatients with active RA (>/=3 swollen and tender joints and C-reactive protein > 10 mg/L) took dexamethasone (1.5 mg) at 23:00 hour in the evening. Next day, baseline saliva and plasma samples were collected, CRH was infused at 11:00 hour, and 4 serial blood and saliva samples were collected. Plasma samples were stored at -80 degrees C and a radioimmunoassay performed for saliva and plasma cortisol. Results. All 20 participants showed normal dexamethasone suppression and mounted no response to the CRH challenge. In samples with measurable cortisol, there was a strong correlation between saliva and plasma values (r = 0.876, n = 26, P < .01). Conclusion. No abnormalities were found in the Dexamethasone-CRH test in RA patients in contrast to a previous pilot study. Salivary cortisol measurement may offer an alternative noninvasive technique to plasma cortisol in RA patients in future studies.

The effect of labor on neonatal T-cell phenotype and function.

With increasing interest in the role of fetal programming in child and adulthood diseases, and therefore interest in the measurement of various factors at birth, it is essential to ascertain whether the factors of interest show any gestation- or parturition-associated changes. We have investigated whether mode of delivery influenced T-cell phenotype and function (CD4+) as has been described for monocytes and neutrophils. Interferon-gamma production in response to either the mitogen phytohemagglutinin or anti-CD2/CD3/CD28 F(ab')3 was significantly reduced by neonatal mononuclear cells compared with adult cells but did not differ with mode of delivery at term (normal vaginal delivery versus elective lower-segment cesarean section). Likewise, anti-CD2/CD3/CD28-stimulated IL-2 production by the neonate was lower than adult levels but did not differ with mode of delivery. The expression of common T-cell activation markers (CD25, MHC class II, CD69, CD62L, CD11a, CD44, and CD49d) was examined. Only CD62L (L-selectin) expression was significantly different, with fewer adult T cells expressing this surface antigen compared with neonatal T cells (p < 0.0003), and significantly more T cells from lower-segment cesarean section than normal vaginal delivery were positive for CD62L (p = 0.012). sCD62L levels were significantly lower in cord plasma compared with adult plasma but did not differ with mode of delivery. Thus the phenotype and function of cord blood T cells did not differ greatly with mode of delivery, but possible differences for the marker of interest should always be assessed. Furthermore, although there was no significant difference with mode of delivery for all markers, except CD62L, the variation in the normal vaginal delivery samples, as for the adults, was greater than in the lower-segment cesarean section samples, indicating that the effects of length of labor and stress at delivery may well be relevant.

Immunoregulatory molecules during pregnancy and at birth.

Regulation of the maternal immune response to the fetal allograft is essential for the success of pregnancy and delivery of a well-developed neonate. Numerous mechanisms have been postulated to mediate this. We hypothesised that the potent immunosuppressive molecules TGF-beta1 and IL-10 could contribute to this regulation in the mother and neonate during gestation. In comparison to non-pregnant women, TGF-beta1 and cortisol levels were increased significantly in mid (16-18 weeks) and late pregnancy (>37 weeks, no labour), with levels of both highest in late gestation. In contrast, IL-10 levels were significantly lower in maternal plasma in mid-gestation compared with that from late pregnancy and from non-pregnant women. TGF-beta1, IL-10 and cortisol were all detectable in umbilical cord blood plasma with TGF-beta1 levels significantly decreased in association with labour in contrast to cortisol levels that increased with labour. IL-10 levels in cord plasma were comparable to those of adults and did not change with mode of delivery. Elevated levels of TGF-beta1, but not IL-10, in the maternal and neonatal circulation could have a role in immunoregulation of the maternal response to the fetal allograft as well as growth and development of the fetus.