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Inflammation and Sjögren's Syndrome

Affecting more than 1.4 million Americans, Sjögren's syndrome is an autoimmune disorder in which immune cells attack and destroy the glands that produce tears and saliva. The hallmark symptoms of the disorder are dry mouth and dry eyes. Sjögren's syndrome is also frequently associated with rheumatic disorders such as rheumatoid arthritis.

T-cell infiltration and markers of immune activation have been noted in both the conjunctiva and lacrimal glands of these patients. Topical anti-inflammatory treatment of patients with dry eye reportedly produces a significant reduction of activated lymphocyte in the conjunctiva, thus demonstrating the potential for anti-inflammatory treatment of dry eyes.

Anti-inflammatory Activity of GLA

Gamma-linolenic acid (GLA) and its precursor linoleic acid (LA) are essential fatty acids found in certain plant seed oils such as black currant seed oil. Oral administration of GLA and LA has been shown to have beneficial effects in the treatment of chronic inflammatory disorders such as rheumatoid arthritis, and several pilot studies conducted in the 1980's suggest that these fatty acids may also benefit the ocular status of patients with Sjögren's.

GLA is metabolized to dihomo-linolenic acid (DGLA), the immediate precursor of PGE1, an eicosanoid with known anti-inflammatory action. In addition, both GLA and DGLA modulate the immune responses by acting directly on T lymphocytes. Researchers from the University of Messina in Italy now report that modest amounts of supplemental GLA and LA raise PGE1 tear content in Sjögren's, and improve signs and symptoms of ocular discomfort in these patients.

Design and Methods

This randomized, double-blind, controlled trial involved 40 patients with primary Sjögren's Syndrome divided into 2 groups. One group received GLA (15 mg) and LA (112 mg) twice daily for 1 month (GLA group), while the other group received placebos. Subjects underwent 3 examinations: baseline (T0), after 1 month (T1), and 15 days after treatment was suspended (T2). At each exam, the following tests were performed: tear sampling from the inferior meniscus, TBUT, fluorescein stain of the ocular surface, and tear basal secretion. A symptom score was also obtained each time. PGE1 was evaluated by enzyme immunoassay, and PGE1 content of tears was the primary endpoint.

Results

Tear PGE1 levels were significantly increased in the GLA group after 1 month of treatment. Fifteen days after treatment was halted, a significant reduction of the PGE1 levels toward baseline was observed. The symptom score was significantly lower in the GLA group after 1 month, with several symptoms (burning, foreign body sensation and dryness) remaining improved after treatment was stopped. The corneal fluorescein stain in this group also showed a significant improvement after the first month, which was sustained 15 days after treatment cessation.

No statistically significant differences were found for the other tests. In contrast to the GLA group, no statistically significant changes were noted in the placebo group at all examination time points. These results are summarized in the table below (group 1 = supplemented; group 2 = placebo).

Conclusions

According to the authors, these results indicate that supplemental GLA and LA effectively increases PGE1, an indicator of anti-inflammatory activity, improves ocular surface status and reduces dry eye symptoms.

Reference
Aragona P, et al. Systemic omega-6 essential fatty acid treatment and PGE1 tear content in Sjogren's syndrome patients. Invest Ophthalmol Vis Sci 46:4474-9, 2005.