Ch. Wang et al., Upregulation of inducible nitric oxide synthase and cytokine secretion in peripheral blood monocytes from pulmonary tuberculosis patients, INT J TUBE, 5(3), 2001, pp. 283-291
Citations number
51
Categorie Soggetti
Cardiovascular & Respiratory Systems
Journal title
INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE
SETTING: Peripheral blood monocytes (PBM) are the main source of alveolar m
acrophages, which have an upregulation of inducible nitric oxide synthase (
iNOS) in pulmonary tuberculosis (TB). TNF-alpha and IL-1 beta are thought t
o be involved in the immune response to mycobacterial infection.
OBJECTIVE: To identify whether iNOS expression and cytokine release of PBM
are upregulated and have a connection in TB infection.
DESIGN: The expression of iNOS immunoreactivity on PBM from TB patients and
normal subjects was measured by loading with anti-macrophage iNOS polycolo
nal primary antibody analyzed by Row cytometry. Expression of iNOS mRNA in
PBM was detected by RT-PCR. The spontaneous generation of nitrite and cytok
ines (IL-1 beta and TNF-alpha) by cultured monocytes was also determined.
RESULTS: Compared to normal subjects, iNOS immuno-reactivity, the capacity
for spontaneous nitrite generation and the level of TNF-alpha or IL-1 beta
secretion of PBM were significantly higher in TB patients. The amount of ni
trite, TNF-alpha and IL-1 beta released from PBM of TB patients was inhibit
ed by NG-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of NOS. Th
e level of iNOS immunoreactivity on PBM was highly correlated with nitrite
generation both in all the subjects studied and in TB patients alone. Spont
aneous TNF-alpha production showed a stronger correlation with nitrite prod
uction than with IL-1 beta.
CONCLUSION: The NO and cytokine synthase activities of monocytes appear to
be concomitantly upregulated in response to mycobacterial infection. The en
hanced NO generation by monocytes in TB patients may play an autoregulatory
role in amplifying the synthesis of proinflammatory cytokines.