The end of the road for the tryptophan depletion concept in pregnancy and infection

نویسندگان

  • Abdulla A.-B. Badawy
  • Aryan M.A. Namboodiri
  • John R. Moffett
چکیده

We hypothesize that: (1) L-tryptophan (Trp) is greatly utilized and not depleted in pregnancy; (2) fetal tolerance is achieved in part through immunosuppressive kynurenine (Kyn) metabolites produced by the flux of plasma free (non-albumin-bound) Trp down the Kyn pathway; (3) the role of indoleamine 2,3-dioxygenase (IDO) in infection is not related to limitation of an essential amino acid, but is rather associated with stress responses and the production of Kyn metabolites that regulate the activities of antigen presenting cells and T-cells, as well as increased NAD(+) synthesis in IDO-expressing cells; (4) Trp depletion is not a host defence mechanism, but is a consequence of Trp utilization. We recommend that future studies in normal and abnormal pregnancies and in patients with infections or cancer should include measurements of plasma free Trp, determinants of Trp binding (albumin and non-esterified fatty acids), total Trp, determinants of activities of the Trp-degrading enzymes Trp 2,3-dioxygenase (TDO) (cortisol) and IDO (cytokines) and levels of Kyn metabolites. We also hypothesize that abnormal pregnancies and failure to combat infections or cancer may be associated with excessive Trp metabolism that can lead to pathological immunosuppression by excessive production of Kyn metabolites. Mounting evidence from many laboratories indicates that Trp metabolites are key regulators of immune cell behaviour, whereas Trp depletion is an indicator of extensive utilization of this key amino acid.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Indoleamine 2,3-Dioxygenase and Immunological Tolerance during Pregnancy

Indoleamine 2,3-dioxygenase (IDO), an enzyme involved in the catabolism of tryptophan, is expressed by a variety of cells and tissues such as macrophages, dendritic cells, cells of the endocrine system and by the placenta. IFN- γ is the main inducer of this enzyme. IDO acts as an important defense mechanism of innate immunity against pathogens. It also has tumor suppressive activity and prolong...

متن کامل

The tryptophan utilization concept in pregnancy

The decrease in maternal plasma total (free + albumin-bound) tryptophan (Trp) during the third pregnancy trimester is attributed to induction of indoleamine 2,3-dioxygenase (IDO). When measured, free [Trp] is increased because of albumin depletion and non-esterified fatty acid elevation. The Trp depletion concept in pregnancy is therefore not supported because of incorrect interpretation of cha...

متن کامل

Effect of Tryptophan Supplementation in Protein Deficient Diets on Performance, Gut Development and Immune Responses in Broiler Chickens

The current trial was conducted to investigate effects of tryptophan (Trp) supplementation in crude protein (CP) deficient diets on performance, gut development and immune responses in broiler chickens. A total of 420 day-old broiler chicks (Ross 308) were assigned to one of 6 dietary treatments, ‎comprising 5 replicates in a completely randomized design including: 1) ‎control diet (CTL) (diet ...

متن کامل

The impact of COVID-19 during pregnancy on fetal brain development

The development of the brain as the most complex structure of the human body is a long process that begins in the third week of pregnancy and continues until adulthood and even until the end of life (1). Human brain myelination begins one to two months before birth in the visual system and eventually lasts until the age of two in other sensory systems and then the motor systems (4). Processes a...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 130  شماره 

صفحات  -

تاریخ انتشار 2016