Genetic influence on cytokine production and fatal meningococcal disease
- PMID: 9111542
- DOI: 10.1016/s0140-6736(96)06413-6
Genetic influence on cytokine production and fatal meningococcal disease
Erratum in
- Lancet 1997 Mar 1;349(9052):656. Vandenbrouke JP [corrected to Vandenbroucke JP]
Abstract
Background: To assess the genetic influence on cytokine production and its contribution to fatal outcome, we determined the capacity to produce tumour necrosis factor-alpha (TNF alpha) and interleukin-10 (IL-10) in families of patients who had had meningococcal disease.
Methods: We studied 190 first-degree relatives of 61 patients with meningococcal disease; we also studied 26 monozygotic twins. Production of cytokines was determined during endotoxin stimulation of whole-blood samples ex-vivo. Heritability was estimated in a pedigree-based maximum-likelihood model. DNA was typed for the G to A transition polymorphisms at position -308 and -238 in the TNF gene promoter.
Findings: Heritability in monozygotic twins was 0.60 for the production of TNF and 0.75 for the production of IL-10. Families with low TNF production had a tenfold increased risk for fatal outcome (OR 8.9, 95% CI 1.8-45), whereas high IL-10 production increased the risk 20-fold (19.5, 2.3-165). Families with both characteristics had the greatest risk. The transition polymorphisms in the TNF gene promoter were not associated with outcome.
Interpretation: Genetic factors substantially influence production of cytokines. An innate anti-inflammatory cytokine profile may contribute to fatal meningococcal disease.
Comment in
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Genetic influence on cytokine production in meningococcal disease.Lancet. 1997 Apr 19;349(9059):1176. doi: 10.1016/s0140-6736(05)63055-3. Lancet. 1997. PMID: 9113037 No abstract available.
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Genetic influence on cytokine production in meningococcal disease.Lancet. 1997 Jun 28;349(9069):1912-3. doi: 10.1016/s0140-6736(05)63910-4. Lancet. 1997. PMID: 9217780 No abstract available.
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