Genetic variation in pro-inflammatory cytokines and  meningococcal sepsis.
OBJECTIVE
Pro-inflammatory cytokines are an essential component of host defence in patients who are susceptible to meningococcal disease. This review summarizes what is currently known about genetic variations in genes encoding these defensive proteins and focuses on recent work investigating the potential role polymorphisms may play insusceptibility and severity of the disease.


RESULTS
A recently developed porcine model revealed significant cytokine derangement early in severe meningococcal sepsis raising the suggestion of a causative role for maladaptive cytokine release in the disease course. In patients who survive septic shock caused by the meningococcus there is a low innate production capacity for interleukin-1beta. Several polymorphisms have been identified in genes encoding for pro-inflammatory cytokines, and recently studies have shown association with susceptibility to infection in polymorphism at both IL-1RA (+2018) and TNF (-308).


CONCLUSIONS
Recent work is adding to the growing evidence that genetic variation in pro-inflammatory cytokines has a role in susceptibility and survival in meningococcal disease. However, data need to be interpreted with caution as there are many confounding factors, sample sizes are often small and there are challenges in identifying suitable control groups.
Deasy
Alice
A
Department of Infection & Immunity, Sheffield School of Medicine and Biomedical Science, Royal Hallamshire Hospital, Sheffield, UK.
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Robert C
RC
D016207:Cytokines / Q000235:genetics* / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008589:Meningococcal Infections / Q000235:genetics* / Q000276:immunology*; D011110:Polymorphism, Genetic; D018805:Sepsis / Q000235:genetics* / Q000276:immunology*
D016207:Cytokines