Enhanced nitric oxide production and expression of inducible nitric oxide synthase in systemic lupus erythematosus patients

الملخص EN

Objective: This study was done aiming to evaluate the level of nitrate/nitrite (N/N) in the sera of Systemic Lupus Erythematosus (SLE) patients and to determine the possibility of finding a correlation between these end products of nitric oxide (NO) and disease activity.

Also, to find whether there is increased expression of either constitutive nitric oxide synthase (cNOS) or inducible nitric oxide synthase (iNOS) in skin biopsies of these patients.

Methods: The level of serum N/N was assessed in twenty-five female SLE patients who were followed-up for a year and had at least one flare during this period.

This was compared with ten healthy controls.

Lupus disease activity was determined with the physician’s global assessment (PGA), the lupus activity index (LAI) and the SLE disease activity index (SLEDAI).

Skin biopsy samples from six active SLE patients were evaluated immunohisto-chemically, using monoclonal antibodies for endothelial cell and keratinocyte cNOS and iNOS.

Results: Serum level of N/N was significantly elevated in SLE patients in the pre-flare period as compared to controls (p<0.05) and was highly significantly elevated in the flare period when compared to the controls (p<0.001).

There was a statistically significant positive correlation between serum N/N levels in the SLE group and disease activity (SLEDAI and LAI).

Renal flare showed a significant correlation with N/N serum levels.

Immunohistochemical analysis of the skin biopsy samples using specific monoclonal antibodies to endothelial cNOS and iNOS revealed no expression of the cNOS in the vascular endothelium or keratinocytes.

In contrast, there was markedly increased endothelial cell expression of iNOS, and definite immunostaining for endothelial cell iNOS.

There was also definite keratinocyte expression of iNOS in all specimens.

Conclusion: There is enhanced NO production as indicated by increased serum levels of N/N in SLE patients.

The latter also correlated with lupus disease activity.

The role of NO in the complex immune interactions of lupus remains unclear.

Due to the relative ease of this assay, measures of serum N/N appear to be a potentially useful laboratory measure of lupus disease activity.

Two potential sources of excessive NO production in SLE are endothelial cells and keratinocytes.

These cells over express iNOS and provide novel and unexpected insights into the inflammatory processes characteristic of SLE.