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Arginine as an adjuvant to chemotherapy improves clinical outcome in active tuberculosis

¹ Dept of Medical Microbiology, Faculty of Health Sciences, Linköping University, Linköping, ² Dept of Infectious Diseases, Karolinska Hospital, Stockholm, and ³ Microbiology and Tumour Biology Centre, Karolinska Institute, Stockholm, Sweden. ⁴ Armauer Hansen Research Institute (AHRI), Addis Ababa, and ⁵ Gondar College of Medical Sciences (GCMS), Gondar, Ethiopia

CORRESPONDENCE: T. Schön, Dept of Medical Microbiology, Faculty of Health Sciences, Linköping University, SE-581 85, Linköping, Sweden. Fax: 46 13224789. E-mail: tschon@telia.com

Keywords: arginine, human immunodeficiency virus, Mycobacterium tuberculosis, nitric oxide, tuberculosis, tumour necrosis factor-

Received: October 2, 2002
Accepted November 14, 2002

This work was supported by SAREC (Swe-1999-267), the Swedish Heart and Lung Foundation (20041594) and the Swedish Research Council.

Nitric oxide (NO) is involved in the host defence against tuberculosis (TB). Patients with TB exhibit increased catabolism and reduced energy intake. Thus the hypothesis for this study was that restoring a relative deficiency in the amino acid arginine, the substrate for mycobactericidal NO production, would improve the clinical outcome of TB by increasing NO production.

In a randomised double-blind study, patients with smear-positive TB (n=120) were given arginine or placebo for 4 weeks in addition to conventional chemotherapy. Primary outcomes were sputum conversion, weight gain, and clinical symptoms after week 8. Secondary outcomes were sedimentation rate and levels of NO metabolites, arginine, citrulline, and tumour necrosis factor-.

Compared with the human immunodeficiency virus (HIV)–/TB+ placebo group, the HIV–/TB+ patients in the arginine group showed significant improvement, defined as increased weight gain, higher sputum conversion rate and faster reduction of symptoms, such as cough. The arginine level increased after week 2 in the HIV–/TB+ arginine group (100.2 µM (range 90.5–109.9) versus 142.1 µM (range 114.1–170.1)) compared with the HIV–/TB+ placebo group (105.5 µM (range 93.7–117.3) versus 95.7 µM (range 82.4–108.9)). HIV seroprevalence was 52.5%. No clinical improvement or increase in serum arginine was detected in arginine supplemented HIV+/TB+ patients compared with placebo.

Arginine is beneficial as an adjuvant treatment in human immunodeficiency virus-negative patients with active tuberculosis, most likely mediated by increased production of nitric oxide.