Specific immunotherapy normalizes tryptophan concentrations in patients with allergic rhinitis.

BACKGROUND/AIMS: An immune shift towards Th2-type immunity seems to be critical in the pathogenesis of allergic asthma and rhinitis. In a previous study, we found higher serum tryptophan concentrations in patients with seasonal tree or grass pollen rhinoconjunctivitis who underwent specific immunotherapy (SCIT) than in controls, and those with the highest levels at baseline responded less well to SCIT. In the present study, we examined whether 'booster immunotherapy' after cessation of SCIT had any influence on tryptophan metabolism during follow-up. METHODS: Serum concentrations of tryptophan, kynurenine and neopterin were assayed in 19 patients (mean age: 26.2 years; 6 females) allergic to grass and/or tree pollen before and after they had received a booster immunotherapy with 4 injections of an allergoid vaccine (Pollinex Quattro; Bencard Vienna, Austria) over 8 ± 3 months outside the pollen season. RESULTS: Serum tryptophan and kynurenine concentrations decreased after booster immunotherapy (mean ± SD, before immunotherapy: 81.1 ± 14.2 µmol/l, after immunotherapy: 61.4 ± 20.9 µmol/l and before immunotherapy: 2.25 ± 0.44, after immunotherapy: 1.69 ± 0.70 µmol/l, respectively; both p < 0.01); this was especially true in those responders who also tended to have lower baseline kynurenine concentrations as compared with nonresponders (p = 0.05). Finally, a correlation between changes in tryptophan metabolism and neopterin concentrations was observed after immunotherapy. CONCLUSIONS: The decrease in tryptophan and kynurenine concentrations following booster immunotherapy in hay fever patients strengthens the hypothesis that tryptophan metabolism might be involved in the course of allergic responses. However, it is still unclear whether the abnormal tryptophan metabolism in pollinosis patients is related to indoleamine 2,3-dioxygenase and/or to a specific cytokine background.

Maternal and early life exposure to manganese in rural Bangladesh.

Manganese exposure and biomarker concentrations during early pregnancy and lactation were investigated in 408 women living in an area with elevated concentrations of both arsenic and manganese in drinking water derived from wells. About 40% of the water samples had manganese concentrations above the World Health Organization's guideline value and showed a strong inverse correlation with arsenic concentrations. Water manganese was found to correlate to urine concentrations, but not to blood or breast milk concentrations. No correlations were found among manganese concentrations in urine, blood, or breast milk. Compared to other populations, manganese concentrations in both urine and blood, but not breast milk, were elevated in the Bangladeshi women and more similar to those of occupationally exposed groups. The lack of associations with water manganese is likely due to variable exposure via water and food, and differences in bioavailability, as well as a complex and/or strict regulation of intestinal manganese absorption, in turn being influenced by nutritional as well as physiological and genetic factors. The results indicate that elevated maternal manganese exposure does not necessarily lead to exposure of breast-fed infants, stressing the importance of breast feeding in high manganese areas. However, the implications of fetal exposurefrom elevated maternal exposure need further investigation.

High serum tryptophan concentration in pollinosis patients is associated with unresponsiveness to pollen extract therapy.

BACKGROUND/AIMS: The immunologic background of allergic asthma and rhinitis includes a preponderance of Th2-type immunity. In parallel, Th1-type immune response is suppressed by Th2-type cytokines. As a consequence, biochemical pathways triggered by Th1-type cytokine interferon-gamma, such as tryptophan degradation by indoleamine 2,3-dioxygenase and neopterin production, might be altered. We examined whether they are related to the outcome of hyposensitization therapy in atopic patients. METHODS: In serum specimens of 44 atopic patients (18 women, 26 men) before any specific immunotherapy, tryptophan and kynurenine concentrations were measured by HPLC, and the kynurenine to tryptophan ratio (kyn/trp) was calculated. Neopterin concentrations were measured by ELISA. Results were compared with concentrations in 38 serum specimens from healthy blood donors and with the outcome of specific subcutaneous immunotherapy in atopics: on clinical grounds, 27 patients were classified as responders, and 17 patients as non-responders. RESULTS: Serum tryptophan concentrations were higher in atopics (84.3 +/- 24.4 microM) than in blood donors (57.9 +/- 7.46 microM; p < 0.001), kynurenine and kyn/trp were not different between the 2 groups. All of the neopterin concentrations measured in patients were <8.7 nM, the upper limit of the normal. Non-responders to subcutaneous immunotherapy had significantly higher tryptophan concentrations (95.7 +/- 27.0 microM) than responders (77.1 +/- 19.9 microM; p = 0.01). No other marker concentrations differed between the groups. CONCLUSIONS: The measurement of serum tryptophan may present an option to predict the outcome of pollen extract therapy. Higher tryptophan levels may result from lower indoleamine 2,3-dioxygenase activity in atopics. However, this possible relationship needs to be confirmed in further studies.