COMPARTMENTALIZED CYTOKINE PRODUCTION WITHIN THE HUMAN LUNG IN UNILATERAL PNEUMONIA

The in situ inflammatory response developing in the human lung during a localized bacterial infection was studied in 15 patients with unilat eral community-acquired pneumonia (CAP). The local response in the inv olved lung was compared with that in the contralateral, noninvolved lu ng as well as with the systemic blood response. Eight healthy voluntee rs served as control subjects. Concentrations of tumor necrosis factor -alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) were measured by ELISA in bronchoalveolar lavage (BAL) fluids ( n = 15), serum (n = 15), and alveolar macrophage and monocyte culture supernatants (n = 8). The concentrations of TNF-alpha, IL-beta and IL- 6 in BAL fluid were significantly higher in the involved lung than in the paired noninvolved lung (p less than or equal to 0.01) or in healt hy subjects (p less than or equal to 0.02, p less than or equal to 0.0 1, and p less than or equal to 0.001, respectively). Serum IL-6 concen trations were higher in patients than in control subjects, whereas IL- 1 beta and TNF-alpha concentrations did not differ in the two groups. Alveolar macrophages from the involved lung spontaneously released hig her concentrations of IL-1 beta, IL-6, and TNF-alpha (p less than or e qual to 0.05) than did macrophages from the noninvolved lung, which se rved as controls. However, macrophages were hyporesponsive in terms of cytokine production to further stimulation by lipopolysaccharide (LPS ) in the noninvolved and involved lung compared with controls, whereas peripheral blood monocytes were not. Our results suggest that during unilateral CAP, the inflammatory response is compartmentalized within the human lung and limited to the site of infection with respect to th e production of TNF-alpha, IL-1 beta, and IL-6.