Clinical Improvement in Chronic Fatigue Syndrome Associated with Enhanced Natural Killer Cell Mediated Cytotoxicity: The results of a pilot study with Isoprinosine®

A. Kumar(1), E. Turgonyi(2), B. Hyde(3), C. Galvis(1), W. Lim(1) and F. Diaz-Mitoma(1)

(1)Departments of Pediatrics, Division of Virology, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa; (2)Newport Pharmaceuticals Ltd., Ireland; and (3)Nightingale Research Foundation, Ottawa, Ontario, Canada.

Chronic fatigue syndrome (CFS) is associated with several immune abnormalities, such as decreased natural killer (NK) cell mediated cytotoxicity and dysregulated production of cytokines.

The clinical impact of Isoprinosine® (immunomodulator / antiviral) on various immune functions in a total of 16 CFS patients diagnosed according to the CDC CFS definition was evaluated. Patients were followed for 28 weeks. Clinical improvement based on the clinical staging was observed in 6 out of 10 patients (60%).

CFS patients at baseline compared to normal controls exhibited a significantly decreased NK activity as well as decreased mitogen-induced production of IL-10, IL-12 and IFN-g in PBMC. The clinically improved patients showed a significantly enhanced NK activity [LU(5 and 15% ) / 106 ] which correlated with the duration of the treatment (p<0.03). A significant increase in IL-12 production by T cell mitogen stimulated PBMC was observed in clinically improved patients treated for 28 weeks compared to the patients on placebo (p < 0.02). Treatment with Isoprinosine® for 12 weeks did not appreciably influence the production of IL-1-á and IL-10. However, discontinuation of treatment resulted in enhanced production of both IL-1-á and IL-10 only in clinically improved patients. When treatment was started again at week 16, significantly decreased production of these two cytokines was observed. Treatment with Isoprinosine® for prolonged periods (28 weeks) also resulted in the enhanced number of CD4+ T helper cells and CD4+, HLA-DR+ T cell number in peripheral blood only in clinically improved patients. These results suggest the clinical efficacy of Isoprinosine® and its potential to enhance NK cell activity.

In view of the small number of patients, further studies are required to investigate the contribution of Isoprinosine®-mediated immune effects to the pathogenesis of CFS.

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