Although biopsies of salivary and lacrimal glands from patients with Sjögren's syndrome (SS) have focal lymphocytic infiltrates and partial destruction of glandular secretory units (acinar and ductal structures), the degree of dryness is beyond that expected for the level of glandular destruction. The failure to exhibit adequate secretory function is not due simply to the destruction of neural innervation to the residual glandular elements or the absence of receptors for acetylcholine on the glandular cells. It is likely that release of cytokines by lymphocytes and glandular cells (especially interleukin-1, interleukin-6 and tumor necrosis factor alpha), autoantibodies and metalloproteinases lead to decreased release of neurotransmitters and decreased response of the residual glandular cells to available neurotransmitters. The ability to modulate immune response and stimulate residual glandular elements provides new therapeutic opportunities for Sjögren's patients.
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