Cognition, MRS neurometabolites, and MRI volumetrics in non-neuropsychiatric systemic lupus erythematosus: preliminary data.

OBJECTIVE: To correlate cognitive dysfunction with structural and neurometabolic brain findings in patients with non-neuropsychiatric systemic lupus erythematosus (non-NPSLE). BACKGROUND: Over 25% of non-NPSLE patients have cognitive dysfunction, but the cerebral basis of this observation is not well understood. METHOD: Seven patients with non-NPSLE and seven control subjects were given a series of neuropsychological tests and neuroimaging with magnetic resonance imaging and magnetic resonance spectroscopy. Analyses of cognitive function and structural and neurometabolic measures of the brain were performed. RESULTS: Compared with controls, the non-NPSLE patients were significantly impaired on a global cognitive impairment index (CII). No significant differences between the groups were found in choline/creatine (Ch/Cr), N-acetylaspartic acid/Cr, or hippocampal volumes. Ch/Cr was highly associated with CII across the sample. CONCLUSIONS: This is the first study to correlate cognitive impairment with an increase in Ch/Cr ratio among patients with SLE. These results, although preliminary, suggest that changes in cerebral white matter may be important in determining the subtle cognitive impairment that may occur in patients with SLE, even in the absence of neuropsychiatric symptoms.

Immunomodulatory effects of melatonin in asthma.

Patients with nocturnal asthma demonstrate circadian variations in airway inflammation. We hypothesized that melatonin, a circadian rhythm regulator, modulates circadian inflammatory variations in asthma. The effect of melatonin stimulation on peripheral blood mononuclear cell cytokine production was evaluated at 4:00 P.M. and 4:00 A.M. in normal control subjects, patients with nocturnal asthma, and patients with non-nocturnal asthma. Melatonin was proinflammatory, causing significantly increased production of interleukin-1, interleukin-6, and tumor necrosis factor-alpha at 4:00 P.M. and 4:00 A.M. in all subject groups (range, 12.8 +/- 3.3 to 131.72 +/- 16.4%, p < or = 0.0003). The observed increases in cytokine production did not change between 4:00 P.M. and 4:00 A.M. in control subjects or in patients with nocturnal asthma (p > 0.05, both cases). At 4:00 P.M., the cytokine response to melatonin of patients with nocturnal asthma was greater than that of control subjects or patients with non-nocturnal asthma and did not change significantly at 4:00 A.M. At 4:00 P.M., the cytokine response of patients with non-nocturnal asthma was less than that of patients with nocturnal asthma and rose significantly at 4:00 A.M. (p = 0.0001, all comparisons). Melatonin is proinflammatory in both patients with asthma and healthy subjects. Patients with nocturnal asthma demonstrate the largest daytime cytokine response and cannot be further stimulated at 4:00 A.M., suggesting chronic overstimulation in vivo. These results suggest differential immunomodulatory effects of melatonin based on asthma clinical phenotype and may indicate an adverse effect of exogenous melatonin in asthma.