Opening the flood gates - Interferon-alpha treatment for Sjogren's syndrome

Interferon (IFN)-alpha is the main IFN produced in response to viral infect ion. Low levels of IFN alpha can be detected in nasal secretions after expo sure to viruses in vivo. Radioimmunoassay has shown that endogenous IFN alp ha is low in children, reaches a peak in young adults, and gradually declin es with aging. Importantly, this endogenous IFN alpha is significantly decr eased in patients with Sjogren's syndrome (SS). IFN alpha has been tested a s a therapeutic agent in patients with SS. Intramuscular human leucocyte IF N alpha increases saliva production significantly in patients with SS. Impr ovements have been noted in lacrimal function and in dryness symptoms. Sinc e IFN alpha infrequently induces autoimmune phenomena and high dose IFN alp ha treatment sometimes has a serious adverse event profile, treatment focus has shifted to use of low dose orally-administered IFN alpha. In a single- masked controlled trial, 60 patients with SS randomly received natural huma n IFN alpha 150IU 3 times a day in an oral lozenge formulation or sucralfat e as control for 6 months. At study end, 15 (50%) of the 30 IFN alpha-treat ed patients had saliva production increases at least 100% above baseline. I FN alpha treatment was well tolerated and no patients withdrew. Labial mino r salivary gland biopsies indicated significant decreases in lymphocytic in filtration accompanied by a significant increase in intact salivary gland t issue after 6 months of treatment. In another 12-week double-masked, random ised, placebo-controlled trial, stimulated saliva production in patients wi th SS receiving IFN alpha lozenges 150IU 3 times daily was significantly in creased. This dosage was also suggestive of benefit for 5 of 7 subjective m easures of oral and ocular comfort. The tolerability profile of these low d ose oral IFN alpha lozenges is excellent; no serious adverse events have be en recorded. Adverse effects were generally mild and there were no clinical ly significant changes in laboratory or clinical safety measures. Low oral doses of natural human IFN alpha thus appear to improve secretory function and relieve dryness in patients with SS without causing significant adverse events. Endogenous or orally administered IFN alpha may activate oropharyn geal lymphoid and epithelial cells and induce production of potent soluble factors which could mediate immunological reactivity. It has been suggested that IFN alpha/beta potentiates clonal expansion and survival of CD8 T cel ls. Stimulating effects have also been demonstrated on natural killer cell activity, which has been shown to be depressed in patients with SS. It is l ikely that some combination of these immunological effects results in anti- inflammatory activity and ameliorates signs and symptoms of SS.