[In vivo and in vitro production of interleukin-1 after febrile convulsions]. / Produzione in vitro e in vivo di interleuchina-1 dopo una convulsione febbrile.

Pathogenesis of febrile convulsions (FC) is still unknown, suggested causes include the role of antidiuretic hormone (ADH). ADH is an endogenous antypyretic and his excessive production of the consequent hyponatraemia may be the cause of FC in children with susceptibility to this type of seizure. Whereas, interleukin-1 (IL1) is a pyrogenic substances and is involved in the release of AVP. Helminen et al. have reported a significantly higher production of IL1 in culture of peripheral blood monocytes stimulated with lipopolysaccharide (LPS) of children with FC than in the others with fever but without convulsions. More recently Lahat et al. have compared plasma and cerebrospinal fluid ILI levels of children with FC with those of children with fever but without convulsions, but they did not find significant differences. The aims of this study were to determine the IL1 levels in vivo and in the supernatants of cultures of peripheral blood mononuclear cells (PBMC) stimulated or not with LPS in children with FC and in children with fever without FC and to evaluate the influence of ADH and diazepam (DZ) on IL1 production. Blood samples for PBMC cultures were obtained from 11 children with FC on the hospital admission, (group 1) and after 48 hours from treatment with DZ (group 2). The production of IL1 was measured by RIA in the supernatants of the PBMC stimulated with LPS, LPS + DDAVP (synthetic vasopressin), LPS + DZ and in vivo in plasma samples. The control groups were constituted by 9 children with fever and without convulsions (group 3), 4 of them were studied at the end of fever too (group 4), and finally by 9 children in good health (group 5). No significant differences were observed. These results do not support the hypothesis that increased production of IL1 is involved in the pathogenesis of FC in children.

Replacement therapy against increased hydroxyurea toxicity in pituitary or adrenal ablated rats.

The main rat adrenocortical hormone, corticosterone, the mineralocorticoid, 11-deoxycorticosterone (DCA) acetate given alone or together (2:1 ratio) twice daily at doses of 2-4 and 1-8 mg/kg, DCA enanthate given in a single injection of 20 mg/kg 0-3 days before the beginning of the experiments and a highly-concentrated injectable extract of the adrenal cortex (4 mg/kg as hydrocortisone twice a day) given by the intramuscular route, delay and partially protect against the increased toxicity following administration of the anticancer drug, hydroxyurea (800 mg/kg/day for 5 days) in adrenalectomized or hypophysectomized animals (80-100% lethality; in control non ablated rats 0-10% lethality). ACTH1-24 (tetracosactide) also proved effective in pituitary ablated rats. The best protection was afforded with the joint administration of corticosterone and DCA (2-4 and 1-2 mg/kg twice a day) or with corticosterone alone at doses (4 mg/kg twice a day) capable of giving plasma levels, six hours after administration on the third day, similar to those observed in non ablated rats receiving HYD in the morning. The adrenocortical hormones may replace a possible unique defense mechanism against drug toxicity, which is lacking in pituitary or adrenal ablated rats.

Antitumour drug toxicity in pituitary or adrenal-ablated rats.

Hypophysectomy or adrenalectomy increase the toxicity of the antitumour drug hydroxyurea (HYD) given by the oral route at daily doses/kg over 5 days, 10 times higher (10 Htd) than that employed in daily schedules for humans (100% and 85% lethality against 0% in intact controls). No differences were found between intact or hypophysectomized rats in their ability to tolerate a 5-day treatment with 1 Htd HYD given orally, 1-10 Htd of procarbazine (i.v.) and cisplatinum (i.v.) at a dose per kg/day equivalent to that recommended for protocols providing daily drug schedules in humans. L-asparaginase (10 Htd) induce 45% lethality in adrenalectomized animals. All the above drugs in intact rats induce significant (p less than 0.01) adrenocortical activation after single, and in the case of hydroxyurea after 5-days, treatment at the above dosages. Replacement therapy with corticosterone may reduce HYD toxicity in adrenalectomized (20% lethality) but less so (90% lethality) in hypophysectomized rats.