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Febrile seizures can be the first sign of epilepsy. In a recent study, patients with temporal lobe epilepsy were reported to carry the interleukin-1beta allele 2 at position -511 more often than healthy control subjects. Because pro-inflammatory cytokines, such as interleukin-1, are well-known inducers of fever and therefore could play an important part in the pathogenesis of febrile seizures, we have, in this study, analyzed the cytokine gene polymorphism of interleukin-1beta at position -511 in children with febrile seizures and control subjects. We found a statistically significant increase in the frequency and the carriage of interleukin-1beta (-511) allele 2 in children with febrile seizures (n = 35) compared with healthy blood donors (n = 400) (P = 0.03 and P = 0.05, respectively). In previous studies, this allele has been connected to increased in vitro production of interleukin-1. Children with febrile seizures may therefore have an increased pro-inflammatory reaction during fever. This pro-inflammatory reaction may also predispose some children to the development of epilepsy.

Epstein-Barr virus (EBV) seronegativity is rare in adults. To examine whether genetic differences would explain this, we studied the genetic polymorphisms of the genes of the interleukin-1 (IL-1) complex in seronegative adults. These cytokines (i.e. IL-1alpha, IL-1beta and IL-1 receptor antagonist, IL-1RA) regulate, in several ways, the inflammatory reactions of the body. In each of these genes there are polymorphic sites and the various alleles differ in their frequency in several diseases of inflammatory nature. In 400 healthy blood donors (from 18 to 60 years of age) there were 20 (5%) seronegative persons. The frequency of allele 2 of the IL-1beta gene (base exchange polymorphism at position -511 from the transcriptional start site) was decreased in the seronegative patients (0.20 versus 0.42 in the seropositive patients, P < 0.05, chi2-test). Moreover, the frequency of allele 2 of the IL-1RA (polymorphism defined by variable numbers of 86-bp repeats in intron 2) was slightly, but not significantly, decreased in the seronegative patients. Alleles of these two loci are known to be associated, but in the seronegative patients this association was abnormal: 11 out of 20 (55%) were of the IL-1RA-2 negative/IL-1beta-2 negative type, while of the seropositive patients, 25% were of this type (P < 0.01, chi2-test). These data suggest that immunological differences, depending on cytokine gene polymorphisms, regulate the resistance to EBV infection.

Interleukin-1 (IL-1) production from peripheral blood mononuclear cells (MNC) was studied in 18 children with septic infection. IL-1 activity was measured from the supernatants of MNC cultures at various times after infection. At the acute stage of infection the IL-1 activity was low (depressed) but rose in early convalescent stage and was normalized at late control after infection. In prolonged infections lasting for 11-25 days the IL-1 activity showed further decline. Rising IL-1 production of MNC in septic infection may be regarded as a good prognostic sign, whereas a declining IL-1 activity may be suggestive of prolonged or complicated course of infection.

Peripheral blood mononuclear cells (MNC) from 27 children with a febrile convulsion were tested for production of interleukin-1 (IL-1) in culture. MNC stimulated with lipopolysaccharide (LPS) showed a significantly increased production of IL-1 when compared to MNC from children without convulsions but with bacterial infections (p less than 0.001), viral infections (p less than 0.005) or no infection (p less than 0.005). Children who had experienced a febrile convulsion were retested several months later; this time the IL-1 production from LPS-stimulated MNC was not different from controls. These results demonstrate that MNC at the time of febrile convulsions have increased sensitivity to LPS and possibly to other IL-1 inducers; the resulting enhanced IL-1 response from sensitized MNC may have a role in the pathogenesis of febrile convulsions.

Interleukin-1 (IL-1) is the key initiator of host responses to infection. We describe here the lipopolysaccharide-(LPS) (20 micrograms/ml) stimulated IL-1 production of peripheral blood monocytes in 2 children with Haemophilus influenzae meningitis. We found a depressed IL-1 production at the acute stage of the infection when the meningitis was most active with return to normal coinciding with clinical recovery. These results show an inverse correlation with acute phase reactants and IL-1 production. Normalization of IL-1 production seems to be a good prognostic sign in bacterial meningitis.

Peripheral blood monocytes from children with severe bacterial infection showed a high level of spontaneous (unstimulated) production of interleukin 1 (IL-1). In viral respiratory or gastrointestinal infections there usually was little or no spontaneous IL-1 production from monocytes, and the values did not differ from those of children with no infections or inflammatory disease. Lipopolysaccharide-induced IL-1 production from monocytes was slightly but not significantly greater in bacterial infections than in viral infections and controls. Tuberculin (purified protein derivative)-induced IL-1 production from monocytes of patients with viral infections was significantly less than in bacterial infections and also slightly less than in controls. These results indicate that systemic bacterial infections activate spontaneous release of IL-1 from monocytes whereas uncomplicated viral infections usually do not. Tuberculin-inducible IL-1 activity of monocytes appears decreased in viral infections; this might be associated with suppressed cell-mediated immunity in such infections.