Serum kynurenine in rheumatoid arthritis

Spiera, Harry; Vallarino, Ramon

doi:10.1172/jci106043

Cited by 20 publications

(11 citation statements)

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“…The accuracy of serum measurements of L-kynurenine by this and other methods can be affected by several factors, such as the presence of other tryptophan metabolites, the binding of kynurenine and tryptophan to serum proteins, and their excretion rate (44)(45)(46). However, our observations that the levels detected in serum are reduced after administration of 1-MT and are increased following exogenous delivery of L-kynurenine suggest that this method can be used to detect changes in the levels or L-kynurenine in serum samples, although a more detailed assessment is required to address its specificity and sensitivity.…”

Section: Discussionmentioning

confidence: 99%

“…Studies on the role of IDO and tryptophan catabolism in humans have shown reduced levels of tryptophan and increased levels of kynurenine in sera from patients with RA (46,47). With the caveats mentioned above about the measurement of tryptophan and its catabolites in serum, these observations suggest that IDO is also activated in RA and fails to control the pathologic development, similar to our findings that IDO is induced during CIA but is not sufficient to counteract the disease.…”

Section: Discussionmentioning

confidence: 99%

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Indoleamine 2,3 dioxygenase–mediated tryptophan catabolism regulates accumulation of Th1/Th17 cells in the joint in collagen‐induced arthritis

Criado

Šimelyte

Inglis

et al. 2009

Arthritis & Rheumatism

116

104

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Indoleamine 2,3 dioxygenase–mediated tryptophan catabolism regulates accumulation of Th1/Th17 cells in the joint in collagen‐induced arthritis

Criado

Šimelyte

Inglis

et al. 2009

Arthritis & Rheumatism

116

104

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“…Tryptophan may also be displaced from aqueous humor albumin thus decreasing its penetration into lens. Increased urinary excretion of tryptophan metabolites (kynurenine, OH-kynurenine, xanthurenic acid) and lower plasma levels of kynurenine are consistently found in patients with rheumatoid arthritis receiving aspirin (1,18,27,29).…”

Section: Discussionmentioning

confidence: 99%

Aspirin effect on cataract formation in patients with rheumatoid arthritis alone or combined to diabetes

Cotlier

1981

Int Ophthalmol

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The prevalence of cataracts is significantly lower in patients with rheumatoid arthritis receiving aspirin (mean of 2,700 mgs daily for an average of 10.4 years) as compared to the matched population not receiving aspirin. Similarly, fewer cataracts were found among a population with diabetes and rheumatoid arthritis receiving aspirin (mean of 2,340 mgs daily for an average of 8.8 years) as compared to the matched population on no aspirin. The effects of aspirin on cataract formation may result from 1) lowering of plasma tryptophan levels and increased excretion of tryptophan metabolites, 2) inhibition of aldose reductase and sorbitol formation in the diabetic lens, 3) inhibition of tryptophan or kynurenine binding to lens protein.

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“…Rats were anaesthetized with pentobarbitone sodium (Abbott, Queensborough, Kent), 60 mg/kg intraperitoneally, and livers perfused by the method of Hems, Ross, Berry & Krebs (1966) using a semisynthetic medium (Woods, Eggleston & Krebs, 1970) consisting of dialysed bovine serum albumin (2.6 g/100 ml), washed aged human red cells (2.5 g/100 ml) and bicarbonate buffered saline (Krebs & Henseleit, 1932) Spiera & Vallarino (1969). The method developed is based on the principle that after deproteinization, kynurenine can be diazotized and coupled with napthyl ethylene diamine, the coloured product then being extracted into amyl alcohol and back-extracted into dilute sulphuric acid to be read at 560 nM on a spectrophotometer (Joseph, 1973).…”

Section: Methodsmentioning

confidence: 99%

Tryptophan Metabolism in the Isolated Perfused Liver of the Rat: Effects of Tryptophan Concentration, Hydrocortisone and Allopurinol on Tryptophan Pyrrolase Activity and Kynurenine Formation

Green

Woods

Joseph³

1976

British J Pharmacology

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1 The effect of tryptophan concentration on the rate of kynurenine appearance and tryptophan disappearance in the medium perfused through the isolated liver of the rat has been investigated. The effect of pretreatment of the rat with hydrocortisone or allopurinol was also examined, together with the effects of these treatments on liver tryptophan pyrrolase activity measured in vitro at the beginning and end of perfusion. 2 Hydrocortisone (5 mg/kg) injection 3 h before perfusion resulted in a four-fold increase in kynurenine production by the liver during perfusion with a medium containing either 0.1 mmol/l or 1.0 mmol/l tryptophan. Injection of allopurinol (20 mg/kg) together with hydrocortisone and addition of allopurinol (4 mg/100 ml) to the medium abolished the hydrocortisone-induced rise of kynurenine in the 0.1 mmol/l tryptophan medium but not the 1.0 mmol/l tryptophan medium. 3 Injection of cycloheximide (30 mg/kg) with hydrocortisone (5 mg/kg) 3 h before perfusion inhibited the hydrocortisone-induced rise of kynurenine production and the increase in pyrrolase activity measured in vitro both before and at the end of perfusion with 1.0 mmol/l tryptophan. This last result suggests that protein synthesis is involved not only in hydrocortisone induction of pyrrolase but also in substrate induction. 4 Kynurenine production in the 1.0 mmol/l tryptophan medium was less in both saline-and hydrocortisone-treated older rats (335-450 g) compared to younger rats (180-220 g). In agreement with a previous study, pyrrolase activity in vitro was also lower in both saline-and hydrocortisonetreated older rats at the beginning of the perfusion although activity had risen equally in both young and older rats at the end of perfusion.5 There was little correlation between the rate of tryptophan disappearance from the medium and the activity of tryptophan pyrrolase either as measured in vitro or as indicated by the rate of kynurenine production. 6 In general, the production of kynurenine in the medium at the end of the 60 min perfusion was indicative of in vitro pyrrolase activity at the start of the perfusion. 7 It is concluded that while in vitro pyrrolase assay does not give a quantitative index of kynurenine production, it does provide a qualitative index. Furthermore, if kynurenine production in the isolated perfused liver of the rat is indicative of in vivo pyrrolase activity, then hydrocortisone must induce pyrrolase activity in vivo.

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Serum kynurenine in rheumatoid arthritis

Cited by 20 publications

References 14 publications

Indoleamine 2,3 dioxygenase–mediated tryptophan catabolism regulates accumulation of Th1/Th17 cells in the joint in collagen‐induced arthritis

Indoleamine 2,3 dioxygenase–mediated tryptophan catabolism regulates accumulation of Th1/Th17 cells in the joint in collagen‐induced arthritis

Aspirin effect on cataract formation in patients with rheumatoid arthritis alone or combined to diabetes

Tryptophan Metabolism in the Isolated Perfused Liver of the Rat: Effects of Tryptophan Concentration, Hydrocortisone and Allopurinol on Tryptophan Pyrrolase Activity and Kynurenine Formation

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