The effects of interleukins on adrenal steroidogenesis and their mode of action were studied using cultured rat adrenal cells. The addition of rat interleukin-1 alpha (IL-1 alpha) or rat IL-2 increased corticosterone levels in the medium in a concentration-dependent manner during 24 h of incubation. The minimum, half-maximum, and maximum effective concentrations of both rat IL-1 alpha and rat IL-2 were almost same (approximately 3, 10, and 100 U/ml, respectively). After a latent period, the effect became apparent after 12 h of incubation. Human IL-1 beta and human IL-6 also showed a stimulatory effect on corticosterone production, whereas human IL-2 was inactive in this system. To clarify the cellular mechanism of these stimulatory effects, we measured the levels of prostaglandin E2 (PGE2) and cAMP in the cells and media as well as the corticosterone levels. Corticosterone production stimulated by IL-1 alpha or IL-2 was accompanied by intracellular and extracellular cAMP and PGE2 accumulation. Although the stimulation of both cAMP and corticosterone was observed only after 12 h of incubation, PGE2 levels increased during the first 4 h of incubation. Corticosterone, cAMP, and PGE2 production stimulated by ILs was almost completely blocked by the addition of 0.1 mM aspirin, a cyclooxygenase inhibitor. Lipoxygenase inhibitors, i.e. AA-861, nordihydroguaiaretic acid, and 5,8,11,14-eicosatetrynoic acid, did not abolish corticosterone production stimulated by ILs. Submaximal doses of IL-1 alpha and IL-2 synergistically stimulated PGE2 production, but did not have even additional effects on cAMP and corticosterone levels. On the other hand, submaximal doses of ACTH, which did not significantly affect PGE2 levels, acted synergistically with IL to increase cAMP and corticosterone levels in these cells. These results indicate that 1) IL-1 alpha and IL-2 directly stimulate glucocorticoid synthesis in a dose- and time-dependent manner; 2) a half-maximum effective concentration of ACTH acts synergistically with IL in stimulating glucocorticoidogenesis; 3) the stimulatory process initially requires PGs, followed by the activation of the adenylate cyclase system; 4) although the profiles of steroidogenic action of IL-1 alpha and IL-2 are quite similar, they may exert their effects through different mechanisms in their early steps of PGE2 production; and 5) the low effective concentrations of both cytokines suggest possible physiological or pathophysiological roles of circulating cytokines in the glucocorticoidogenesis under certain conditions.
Summary:Purpose: A population-based survey of childhood epilepsy was undertaken in Okayama Prefecture, Japan, to determine the prevalence rate and the distribution of epilepsies and epileptic syndromes according to the International Classification (ILAE, 1989).Methods: Information on patients younger than 13 years with active epilepsy was collected from medical records. Patients diagnosed with epilepsy according to clinical and EEG findings were put on the list even if those patients had had a single seizure or seizures occurring during febrile episodes.Results: In total, 2,220 cases were identified from a background population of 250,997. The prevalence rate was 8.8 per 1,000. If we exclude patients who had experienced a single seizure or seizures occurring during febrile episodes to compare our results with previous reports, the prevalence rate was 5.3 per 1,000. Of the 2,220 cases, 2,030 (91.4%) were classified into three major categories by ILAE classification. They consisted of 1,556 (76.7%) with localization-related epilepsy, 453 (22.3%) with generalized epilepsy, and 21 (1.0%) with undetermined epilepsy. Of the 2,030 cases, 309 (15.2%) were classified into epileptic syndrome categories, and 84.8% of the total were nonspecific types of epilepsy.Conclusions: The prevalence rate of childhood epilepsy was distributed from 5.3 to 8.8 per 1,000. The appearance rate of various types of epileptic syndromes was low. Most cases could not be classified into the detailed categories of the International Classification (ILAE, 1989). Key Words: PrevalenceChildhood epilepsy-Classification-Epileptic syndromesPopulation-based survey.Population-based surveys of epilepsy have been repeatedly undertaken in many countries. However, the appearance rate or distribution of various types of epilepsies and epileptic syndromes (1) (5) reported on the appearance rate of epileptic syndromes. In these population-based surveys, many types of epileptic syndromes were not detected because the patients numbered fewer than 200. We therefore carried out a population-based survey of childhood epilepsy within a large population in Okayama Prefecture, Japan. SUBJECTS AND METHODSWith December 31, 1999, as the prevalence day, the child population in Okayama Prefecture younger than 13 years was 250,997 (128,452 boys, 9,429-10,869 per year of age; 122,545 girls, 8,975-10,447 per year of age). We determined that the patients who had taken antiepilepAccepted October 8, 2005. Address correspondence and reprint requests to Dr. E. Oka at Asahigawa Rehabilitation Center Jidouin Hospital, Gion Chisaki, Okayama 703-8555, Japan. E-mail: e-oka@jidouin.jp tic medications (AEDs) or who had experienced at least one seizure during the previous 5 years had active epilepsy. If a case with a convulsion during a febrile episode has definite epileptic discharges in interictal EEG, it should be considered to have not only a simple febrile convulsion or a complex febrile convulsion, but also an epileptic seizure occurring during febrile episode.The patients diagnosed...
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