Impairment of beta chemokine and cytokine production in patients with HIV related Pneumocystis jerovici pneumonia.
BACKGROUND
Pneumocystis jerovici pneumonia (PJP) remains a frequent opportunistic infection in HIV infected patients which markedly upregulates HIV replication by mechanisms so far poorly elucidated. PJP triggers the production of proinflammatory mediators with activating effects on HIV. However, anti-inflammatory factors with inhibiting effects on HIV are normally produced in parallel. We postulated that an imbalance of mediators normally controlling HIV replication could underlie its marked increase during PJP.


METHODS
The production of tumour necrosis factor alpha (TNFalpha), interleukins IL-6 and IL-10, and beta-chemokine by bronchoalveolar lavage (BAL) cells recovered from HIV infected patients with and without PJP was compared. The pulmonary viral load was determined and correlations with cytokine and chemokine production were examined.


RESULTS
TNFalpha and IL-6 release was similar in patients with and without PJP but IL-10 and beta-chemokine release was markedly lower in the PJP group (IL-10: p<10(-2), RANTES, MIP-1alpha and MIP-1beta: p<0.001). The pulmonary viral load was markedly higher in patients with PJP (p<0.001) and correlated negatively with levels of MIP-1alpha, RANTES and IL-10 in BAL fluid cells (p<0.05).


CONCLUSIONS
Pulmonary IL-10 and beta-chemokine production is markedly defective in HIV infected patients with PJP, while pulmonary TNFalpha and IL-6 levels are normal. The resulting excess of these latter factors, which are known to upregulate HIV replication, might contribute to the increase in pulmonary viral load and to the more rapid HIV disease progression observed in patients with PJP.
Israël-Biet
D
D
Laboratoire d'Immunopathologie Pulmonaire, UPRES EA220, Université Paris V, Paris, France. dib.laennec@invivo.edu
Esvant
H
H
Laval
A M
AM
Cadranel
J
J
D017088:AIDS-Related Opportunistic Infections / Q000150:complications / Q000378:metabolism*; D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D010949:Plasma; D011020:Pneumonia, Pneumocystis / Q000150:complications / Q000378:metabolism*; D019562:Viral Load
D019742:Chemokines, CC; D016207:Cytokines