title: Interleukin-8 and eicosanoid production in the lung during moderate to severe Pneumocystis carinii pneumonia in AIDS: a role of interleukin-8 in the pathogenesis of P. carinii pneumonia.
abstract: Pneumocystis carinii pneumonia (PCP) may cause severe respiratory distress. This is believed to be partly caused by the accumulation of neutrophils in the lung. Interleukin-8 (IL-8) and leukotriene B4 (LTB4) are potent neutrophil chemo-attractants and activators. Eicosanoids [i.e. prostaglandins (PG) and leukotrienes (LT)] are pro-inflammatory mediators released from arachidonic acid by action of phospholipase A2 (PLA2) and have been implicated in the host response to micro-organisms. Bronchoalveolar lavage (BAL) was performed on patients with PCP as part of a randomized study of adjuvant corticosteroids vs. placebo, in addition to standard antimicrobial therapy. Re-bronchoscopy was offered at day 10. BAL fluid was available for 26 patients who had follow-up bronchoscopy performed. At diagnosis, IL-8 levels were elevated in patients with PCP, compared to healthy controls, and correlated with relative BAL neutrophilia and P(A-a)O2. LTB4 was also elevated in PCP, but failed to correlate with either BAL neutrophilia or P(A-a)O2. PLA2 activity in patients correlated with IL-8 levels and BAL neutrophilia, but not with P(A-a)O2. A trend towards a decrease in IL-8 levels in BAL fluid was detected in the corticosteroid-treated patients from days 0-10, whereas no change was detected in the placebo group. No change in levels of LTB4, LTC4, PGE2, PGF2a and PLA2 were detected cover time in either treatment group. This study establishes a correlation between IL-8, BAL neutrophilia and P(A-a)O2, and suggests a role of IL-8 as a mediator in the pathogenesis of PCP, whereas the role of eicosanoids seems less clear.
authors.affiliation: Department of Infectious Diseases, Hvidovre Hospital, Righospitalet, University of Copenhagen, Denmark.
authors.forename: T L
authors.initials: TL
authors.lastname: Benfield
authors.forename: R
authors.initials: R
authors.lastname: van Steenwijk
authors.forename: T L
authors.initials: TL
authors.lastname: Nielsen
authors.forename: J R
authors.initials: JR
authors.lastname: Dichter
authors.forename: G Y
authors.initials: GY
authors.lastname: Lipschik
authors.forename: B N
authors.initials: BN
authors.lastname: Jensen
authors.forename: J
authors.initials: J
authors.lastname: Junge
authors.forename: J H
authors.initials: JH
authors.lastname: Shelhamer
authors.forename: J D
authors.initials: JD
authors.lastname: Lundgren
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000378:metabolism*; D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D015777:Eicosanoids / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D008168:Lung / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D011239:Prednisolone / Q000627:therapeutic use
chemical_list: D015777:Eicosanoids; D016209:Interleukin-8; D011239:Prednisolone; D010741:Phospholipases A; D054467:Phospholipases A2