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

T. L. Benfield; R. van Steenwijk; T. L. Nielsen; J. R. Dichter; G. Y. Lipschik; B. N. Jensen; J. Junge; J. H. Shelhamer; J. D. Lundgren

doi:10.1016/0954-6111(95)90089-6

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

T. L. Benfield, R. van Steenwijk, T. L. Nielsen, J. R. Dichter, G. Y. Lipschik, B. N. Jensen, J. Junge, J. H. Shelhamer, J. D. Lundgren

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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, PGF_2α and PLA₂ were detected over 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.

Original language	English (US)
Pages (from-to)	285-290
Number of pages	6
Journal	Respiratory Medicine
Volume	89
Issue number	4
DOIs	https://doi.org/10.1016/0954-6111(95)90089-6
State	Published - Apr 1995
Externally published	Yes

Bibliographical note

Funding Information:
We thank the doctors and nurses performing the bronchoscopies, and Mrs Lena Hansen for technical assistance. This study was supported by the Danish National Association Against Lung Disease, the Danish Medical Research Council, the Novo Nordisk Foundation, the Danish Hospital Founda-tion for Medical Research (region of Copenhagen, the Faroe Islands and Greenland), and the Danish AIDS Foundation.

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Benfield, T. L., van Steenwijk, R., Nielsen, T. L., Dichter, J. R., Lipschik, G. Y., Jensen, B. N., Junge, J., Shelhamer, J. H., & Lundgren, J. D. (1995). 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. Respiratory Medicine, 89(4), 285-290. https://doi.org/10.1016/0954-6111(95)90089-6

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. / Benfield, T. L.; van Steenwijk, R.; Nielsen, T. L. et al.
In: Respiratory Medicine, Vol. 89, No. 4, 04.1995, p. 285-290.

Research output: Contribution to journal › Article › peer-review

Benfield, TL, van Steenwijk, R, Nielsen, TL, Dichter, JR, Lipschik, GY, Jensen, BN, Junge, J, Shelhamer, JH & Lundgren, JD 1995, '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', Respiratory Medicine, vol. 89, no. 4, pp. 285-290. https://doi.org/10.1016/0954-6111(95)90089-6

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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, PGF2α and PLA2 were detected over 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.",

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note = "Funding Information: We thank the doctors and nurses performing the bronchoscopies, and Mrs Lena Hansen for technical assistance. This study was supported by the Danish National Association Against Lung Disease, the Danish Medical Research Council, the Novo Nordisk Foundation, the Danish Hospital Founda-tion for Medical Research (region of Copenhagen, the Faroe Islands and Greenland), and the Danish AIDS Foundation.",

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AU - Junge, J.

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N2 - 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, PGF2α and PLA2 were detected over 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.

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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

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