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Leukotriene B4 and lnterleukin-8 in Human Immunodeficiency Virus-related Pulmonary Disease (10)

The BAL fluid IL-8 was elevated in HIV-infected patients with P carinii pneumonia and correlated with the BAL fluid absolute neutrophil count. These data suggest that IL-8 mediates recruitment and activation of neutrophils in P carinii pneumonia and may thereby contribute to the hypoxia seen in this infection. Interleukin-8 also may play a role in P carinii pneumonia associated with other types of immunosuppression. BAL fluid IL-8 levels in two HIV-negative patients who died of P carinii pneumonia were the highest we have measured (data not shown), yet LTB4 was only slightly elevated.
Interleukin-8 production by alveolar macrophages in this disease is an attractive mechanism for neutrophil recruitment. Several groups have shown that alveolar macrophages from patients with P carinii pneumonia demonstrate increased production of cytokines both constituitively and in response to stimulation. Conceivably, IL-8 production in vivo by macrophages exposed to P carinii organisms represents both a local host response to the infection and a mechanism of lung injury. Tumor necrosis factor a and interleukin-1 secretion by activated macrophages also is known to promote IL-8 production by other cells, including fibroblasts and alveolar type II cells. Other neutrophil chemotaxins (C5a, platelet-activating factor) and other cytokines also may be involved. The lack of a statistically significant elevation in the BAL fluid absolute neutrophil count in our patients with P carinii pneumonia probably reflects variability in the data and relatively mild disease in this group; none of these patients died, none required mechanical ventilation, and only one patient (No. 26) had a Pa02 below 70 mm Hg, a recommended cutoff for administering adjunctive corticosteroids for severe P carinii pneumonia.

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