Open AccessInhibition of ex vivo proinflammatory cytokine secretion in fatal Mycobacterium tuberculosis infection
Author(s) -
FRIEDLAND J. S.,
HARTLEY J. C.,
HARTLEY C. G. C.,
SHATTOCK R. J.,
GRIFFIN G. E.
Publication year - 1995
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1111/j.1365-2249.1995.tb03659.x
Subject(s) - ex vivo , proinflammatory cytokine , immunology , tumor necrosis factor alpha , cytokine , mycobacterium tuberculosis , erythrocyte sedimentation rate , immune system , tuberculosis , whole blood , lipopolysaccharide , medicine , stimulation , in vivo , biology , inflammation , pathology , microbiology and biotechnology
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.