HIV-1-related pleural tuberculosis: elevated production of IFN-gamma, but failure of immunity to Mycobacterium tuberculosis.
BACKGROUND
Pleural tuberculosis can resolve spontaneously, suggesting that the inflammatory process may represent a protective immune response. However, pleural tuberculosis is strongly associated with HIV infection. It has been suggested that cell-mediated immune responses may be reduced, and direct bacterial invasion may have a role in pathogenesis, in HIV-positive cases. To test this hypothesis, we compared production of the pro-inflammatory cytokines, interferon (IFN)-gamma and tumour necrosis factor(TNF)-alpha, production of the immunosuppressive cytokine, interleukin (IL)-10, and mycobacterial culture positivity, in HIV-negative and HIV-positive patients with pleural tuberculosis.


METHODS
Cytokine levels were measured in serum and pleural fluid, and in supernatants of blood and pleural fluid stimulated in vitro using mycobacterial antigens. Intracellular IFN-gamma and TNF-alpha production was measured after stimulation with phorbol myristate acetate and ionomycin in vitro.


RESULTS
IFN-gamma was strikingly elevated in serum and pleural fluid in HIV-positive, compared to HIV-negative subjects (P < or = 0.02). TNF-alpha was elevated, but this was not statistically significant. IL-10 levels were higher in serum (P < 0.001), but similar in pleural fluid. IFN-gamma responses to soluble mycobacterial antigen in vitro were reduced in peripheral blood (P = 0.006), but not pleural fluid, of HIV-positive subjects. Intracellular cytokine staining suggested that CD8+ T cells were a major source of IFN-gamma in HIV-positive subjects. The proportion of subjects with a positive culture for Mycobacterium tuberculosis from pleural fluid was higher in the HIV-positive group.


CONCLUSIONS
HIV-positive patients with pleural tuberculosis show elevated production of IFN-gamma, for which CD8+ T cells may be a major source. Mycobacterium tuberculosis can proliferate despite high levels of pro-inflammatory cytokines.
Hodsdon
W S
WS
Medical Research Council Programme on AIDS, Uganda Virus Research Institute, Entebbe, Uganda.
Luzze
H
H
Hurst
T J
TJ
Quigley
M A
MA
Kyosiimire
J
J
Namujju
P B
PB
Johnson
J L
JL
Kaleebu
P
P
Okwera
A
A
Elliott
A M
AM
D000328:Adult; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D018023:HIV Seronegativity / Q000276:immunology*; D006679:HIV Seropositivity / Q000150:complications / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D020382:Interleukin-18 / Q000096:biosynthesis*; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000145:classification; D014396:Tuberculosis, Pleural / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D020382:Interleukin-18; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10