Serum nitric oxide metabolites and disease activity in patients with systemic sclerosis

There is no surrogate marker in serum for defining disease activity in scleroderma (SSc). Nitric oxide (NO), which regulates vasodilation and possesses pro-inflammatory actions, has been implicated in the pathogenesis of SSc. We compared serum NOx (total nitrate and nitrite) level in SSc patients to healthy controls and evaluated its correlation with detailed symptomatology and scoring systems for various organ involvement. Symptoms and physical findings that suggested disease activity in regard to various organs were documented. Lung function test, high-resolution computed tomographic (HRCT) scan of thorax and echocardiography were performed. Serum NO (x) was measured by chemiluminescence. Serum NOx levels in SSc (n=43) were significantly higher (72.4 +/- 47.8 mu M) than age- and sex-matched controls (n=41; 37.1 +/- 13.5 mu M; p < 0.001). Serum NOx were not found to be associated with lung fibrosis defined by lung function parameters or inflammation and fibrosis scores on HRCT. Twenty-two patients were found to have elevated serum NOx level defined as mean +/- 2 SD of normal controls. Logistic regression analysis revealed that age (OR 1.12, p=0.02) and elevated pulmonary arterial pressure (PAP) (n=9; OR 145.3, p=0.01) were predictive factors for elevated serum NOx . Prednisolone use was associated with lower serum NOx level (OR 0.06, p=0.04). Elevated PAP of increasing severity was found to be associated with higher level of serum NOx (p=0.004 by trend). Serum NOx in SSc patients were elevated compared to healthy controls. Serum NOx level was determined by multiple factors including age, prednisolone use, and elevated PAP.