Inhibition of ex vivo proinflammatory cytokine secretion in fatal Mycobacterium tuberculosis infection

Author:

FRIEDLAND J S1,HARTLEY J C2,HARTLEY C G C2,SHATTOCK R J1,GRIFFIN G E1

Affiliation:

1. Division of Communicable Diseases, St. George's Hospital Medical School, London, UK

2. Monze, District Hospital, Monze, Zambia

Abstract

SUMMARY Tuberculosis is characterized by fever, weight loss, a prolonged acute-phase protein response and granuloma formation. These characteristics may partly be due to action of proinflammatory cytokines tumour necrosis factor (TNF), IL-6 and IL-8. We investigated plasma concentrations of these cytokines before and after ex vivo lipopolysaccharide stimulation of whole blood leucocytes from 41 Zambian patients with tuberculosis, 32 of whom were also HIV+. Although patients had a reduced weight, were more anaemic and had higher erythrocyte sedimentation rate compared with controls (all P < 0·0005), clinical and laboratory measurements of disease state were similar in those who died and survivors. In contrast, plasma IL-6 and IL-8 concentrations were higher in patients who died (P < 0·05). There was no detectable cytokine mRNA in unstimulated leucocytes. There was reduced secretion of TNF (P < 0·005 at 2h), IL-6 (P < 0·005 at 8 h) and IL-8 (P < 0·005 at 24 h) after ex vivo stimulation of whole blood leucocytes from patients who died compared with survivors. This was partly due to a soluble inhibitory factor present in plasma. The only additional effect of concurrent infection by HIV with Myco. tuberculosis was decreased IL-6 secretion following ex vivo stimulation of leucocytes. Reduced proinflammatory cytokine release may represent a critical impairment of host immune defences important in determining outcome in tuberculosis.

Publisher

Oxford University Press (OUP)

Subject

Immunology,Immunology and Allergy

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