title: Cytokine activation is predictive of mortality in Zambian patients with AIDS-related diarrhoea.
abstract: BACKGROUND
  Mortality in Zambian AIDS patients is high, especially in patients with diarrhoea, and there is still unacceptably high mortality in Zambian patients just starting anti-retroviral therapy. We set out to determine if high concentrations of serum cytokines correlate with mortality.
  
  
  METHODS
  Serum samples from 30 healthy controls (HIV seropositive and seronegative) and 50 patients with diarrhoea (20 of whom died within 6 weeks) were analysed. Concentrations of tumour necrosis factor receptor p55 (TNFR p55), macrophage migration inhibitory factor (MIF), interleukin (IL)-6, IL-12, interferon (IFN)-gamma and C-reactive protein (CRP) were measured by ELISA, and correlated with mortality after 6 weeks follow-up.
  
  
  RESULTS
  Apart from IL-12, concentrations of all cytokines, TNFR p55 and CRP increased with worsening severity of disease, showing highly statistically significant trends. In a multivariable analysis high TNFR p55, IFN-gamma, CRP and low CD4 count (CD4 count <100) were predictive of mortality. Although nutritional status (assessed by body mass index, BMI) was predictive in univariate analysis, it was not an independent predictor in multivariate analysis.
  
  
  CONCLUSIONS
  High serum concentrations of TNFR p55, IFN-gamma, CRP and low CD4 count correlated with disease severity and short-term mortality in HIV-infected Zambian adults with diarrhoea. These factors were better predictors of survival than BMI. Understanding the cause of TNFR p55, IFN-gamma and CRP elevation may be useful in development of interventions to reduce mortality in AIDS patients with chronic diarrhoea in Africa.
authors.affiliation: Tropical Gastroenterology and Nutrition group, Department of Medicine, University of Zambia School of Medicine, Lusaka, Zambia. zuluisaac@yahoo.com
authors.forename: Isaac
authors.initials: I
authors.lastname: Zulu
authors.forename: Ghaniah
authors.initials: G
authors.lastname: Hassan
authors.forename: Lungowe
authors.initials: L
authors.lastname: Njobvu R N
authors.forename: Winnie
authors.initials: W
authors.lastname: Dhaliwal
authors.forename: Sandie
authors.initials: S
authors.lastname: Sianongo
authors.forename: Paul
authors.initials: P
authors.lastname: Kelly
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000276:immunology / Q000401:mortality*; D000328:Adult; D018791:CD4 Lymphocyte Count; D016207:Cytokines / Q000097:blood*; D003967:Diarrhea / Q000276:immunology / Q000401:mortality*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D011379:Prognosis; D013223:Statistics as Topic; D015024:Zambia
chemical_list: D016207:Cytokines