Pteridine Pathway in Patients with Degenerative Diseases During Short Time Treatment with Low Dose of Meloxicam, as a Non-steroidal Anti-inflammatory Drug

The profiles of unconjugated pteridines such as neopterin and biopterin and of tryptophan metabolism change in many pathologic conditions such as rheumatoid arthritis, malignancies and autoimmune diseases and are related to the release of pro-inflammatory cytokines. However, studies on potential effects of drugs are very limited. This study investigates whether meloxicam, a non-steroidal anti-inflammatory drug, may cause any alteration of the pteridine pathway and tryptophan metabolism in 22 patients who admitted to the Physical and Rehabilitation Medicine outpatient clinic in the Hacettepe University Hospital and suffering from various musculoskeletal pain conditions without systemic inflammation. Urine concentrations of neopterin, biopterin and xanthopterin, and serum concentrations of neopterin, tryptophan, and kynurenine, and the activity of dihydropteridine reductase were measured at the beginning of the therapy and after a 15 days treatment with meloxicam. Average urine concentrations (+/- S.E.M.) of pterins before therapy (neopterin: 263 +/- 15.6 mu mol/mol creatinine, biopterin: 72.4 +/- 13.4 mu mol/mol creatinine, and xanthopterin: 675 +/- 93.0 mu mol/mol creatinine) were not changed during meloxicam therapy (neopterin: 230 +/- 30.7 mu mol/mol creatinine = 88% of baseline, biopterin 115 +/- 26.5 mu mol/mol creatinine = 159% of baseline, and xanthopterin 684 +/- 88.0 mu mol/mol creatinine = 101% of baseline; all differences not significant). The activity of dihydropteridine reductase was 6.02 +/- 0.21 nmol/cytochrome C reduced/min/5 mm disc before and 6.28 +/- 0.18 nmol/cytochrome C reduced/min/5 mm after treatment (= 104% of baseline; p = 0.088). Serum concentrations of neopterin 6.04 +/- 0.33 nmol/L before treatment increased to 6.89 +/- 0.48 nmol/L after treatment (= 114% of baseline; p < 0.05, paired rank test). Likewise serum kynurenine concentrations increased from 1.52 +/- 0.13 mu mol/L to 1.87 +/- 0.14 mu mol/L after treatment (= 123% of baseline; p < 0.01). There was a significant correlation between neopterin and kynurenine concentrations which corresponds with their common background of production, namely immune activation. However, also the mean tryptophan concentration in pretreatment samples 51.4 +/- 3.34 increased to 59.3 +/- 3.34 mu mol/L post-treatment (= 115% of baseline; p < 0.05). The change of kyn/trp was minor (at baseline: 30.4 +/- 2.01, post-treatment: 32.2 +/- 2.47 mu mol/mmol; = 106% of baseline, not significant). Our findings show an influence of meloxicam treatment on neopterin and tryptophan metabolism in patients. However, significant differences were only found in serum but not in urine of patients. In serum, all marker concentrations increased including tryptophan and kynurenine.