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Serum interferon levels were estimated in 67 samples obtained from 47 patients with SLE. Levels were increased in 70% of the samples and 72% of the patients. In the patients with active disease 81% had increased interferon levels, while in the group with clinically quiescent disease 10% had increased levels. In 20 patients retested 3½ months after treatment the changes in interferon levels tended to parallel the changes in clinical disease activity in 80% of cases. Patients with active skin lesions, arthritis, and renal or haematopoietic involvement tended especially to have increased interferon levels. Interferon levels were directly related to ANA titre and inversely related to serum C3 levels, but not related to serum levels of circulating immune complexes or immunoglobulin. The interferon was shown to be of type α. The interferon level can be regarded as one of several parameters reflecting disease activity and may also be related to the prognosis. As it is possible that interferon may be a direct mediator of the pathophysiology of auto-immune disease, we do not recommend the use of interferon or its inducers in the therapy of SLE. [ABSTRACT FROM AUTHOR]

17-β-estradiol (E2) is a steroid hormone involved in neuroprotection against excitotoxicity and other forms of brain injury. Through genomic and nongenomic mechanisms, E2 modulates neuronal excitability and signal transmission by regulating NMDA and non-NMDA receptors. However, the mechanisms and identity of the receptors involved remain unclear, even though studies have suggested that estrogen G-protein-coupled receptor 30 (GPR30) is linked to protection against ischemic injury. In the culture cortical neurons, treatment with E2 and the GPR30 agonist G1 for 45 min attenuated the excitotoxicity induced by NMDA exposure. The acute neuroprotection mediated by GPR30 is dependent on G-protein-coupled signals and ERK1/2 activation, but independent on transcription or translation. Knockdown of GPR30 using short hairpin RNAs (shRNAs) significantly reduced the E2-induced rapid neuroprotection. Patch-clamp recordings revealed that GPR30 activation depressed exogenous NMDA-elicited currents. Short-term GPR30 activation did not affect the expression of either NR2A- or NR2B-containing NMDARs; however, it depressed NR2B subunit phosphorylation at Ser-1303 by inhibiting the dephosphorylation of death-associated protein kinase 1 (DAPK1). DAPK1 knockdown using shRNAs significantly blocked NR2B subunit phosphorylation at Ser-1303 and abolished the GPR30-mediated depression of exogenous NMDA-elicited currents. Lateral ventricle injection of the GPR30 agonist G1 (0.2 μg) provided significant neuroprotection in the ovariectomized female mice subjected to middle cerebral artery occlusion. These findings provide direct evidence that fast neuroprotection by estradiol is partially mediated by GPR30 and the subsequent downregulation of NR2B-containing NMDARs. The modulation of DAPK1 activity by GPR30 may be an important mediator of estradiol-dependent neuroprotection.