IntroductionCellular constituents of the alveolar-capillary wall may be key participants in the recruitment of polymorphonuclear leukocytes to the lung through the generation of the novel neutrophil chemotactic peptide interleukin-8 (IL-8 Invest. 1990Invest. . 86:1945Invest. -1953
The alveolar macrophage (AMO) in its pivotal position for pulmonary host defense may play a prominent role in the orchestration of polymorphonuclear leukocyte (PMN) diapedesis. We demonstrate that the human AMO may participate in these inflammatory events through the production of a novel neutrophil chemotactic factor, interleukin-8 (IL-8). The induction of AMO-derived IL-8 by tumor necrosis factor (TNF), lipopolysaccharide (LPS), and interleukin-1 (IL-1 beta) was shown to be both dose and time dependent. Maximal IL-8 gene expression, as assessed by Northern blot analyses, was achieved with 20 ng/ml and 1 microgram/ml, respectively, for each of the cytokines and LPS. A kinetic study of TNF-, IL-1 beta-, and LPS-treated AMOs showed significant steady-state IL-8 mRNA accumulation post-stimulation at 1 h, peaking by 8 h, with a decline over the next 16 h. Immunohistochemical staining using rabbit anti-human IL-8 antibody demonstrated significant immunolocalization of cell-associated IL-8 antigen at 4 h, with persistence over the next 20 h. Chemotactic bioactivity peaked by 8 h, with continued production over the next 16 h. Chemotactic bioactivity from AMO-conditioned media was inhibited by IL-8 antiserum by 2, 31, 44, and 47%, respectively, for unstimulated control, LPS-, IL-1 beta-, and TNF-treated cells. Preimmune serum had no effect on chemotactic activity. These data support the central role of the AMO in the elicitation of PMNs into the lung via the production of IL-8.
Insufficient evidence exists to support goal-directed therapy with vasopressors and inotropes in the treatment of sepsis syndrome. No definitive recommendations can be made about the superiority of a vasopressor or inotropic agent due to the lack of data. However, it may be that evaluation of vasopressors earlier in sepsis syndrome will yield more promising results. Large, comparative, controlled trials assessing mortality rate and development of multiple organ system dysfunction are needed.
Numerous cytokines are thought to be important in the pathogenesis of granulomatous inflammation and subsequent fibrosis in sarcoidosis. Interleukin (IL)-6 and IL-8, two recently described cytokines with a broad spectrum of proinflammatory effects, could participate in this disease. We obtained bronchoalveolar lavage fluid (BALF) from 16 subjects (13 African-American, three Caucasian) with untreated active pulmonary sarcoidosis and 10 healthy nonsmoking volunteers (nine Caucasian, one African-American). Concentrated BALF was analyzed by an ELISA for IL-6, IL-8, and albumin. The median IL-6 level was 9.8 pg/mg albumin (range, 0-278) for the sarcoid group compared with 0.14 pg/mg (range, 0.14-9.8) in the control subjects (p = 0.001). The corresponding values for IL-8 were 202 pg/mg (range, 35-2179) versus 5.0 pg/mg (range, 0-44) in the control subjects (p < 0.001). Among the sarcoid patients, BALF IL-6 and IL-8 levels correlated with each other (r = 0.96, p < 0.001), and both cytokines correlated with the BALF neutrophil percentage (r = 0.96 and 0.95, respectively; p < 0.001 for both). No difference was detected in IL-8 concentrations as measured by ELISA in culture supernatants of alveolar macrophages obtained from five sarcoid patients and five control subjects. We conclude that IL-6 and IL-8 are elevated in BALF of patients with active sarcoidosis and may be important modulators of the disease process.
Chemotactic cytokines are becoming increasingly recognized as important participants in the coordinate recruitment of specific inflammatory cells. In this manuscript we present data demonstrating that LPS challenged human mononuclear phagocytic cells can express mRNA for neutrophil chemotactic factor/interleukin-8 (NCF/IL-8), but do not express mRNA for monocyte chemotactic protein (MCP). The expression of NCF/IL-8 mRNA was time and dose dependent. This identical stimulus response was also found in peripheral blood neutrophils. These studies demonstrate a disparate production of chemotactic cytokines by macrophages and exemplify the dynamic nature of the chemotactic response.
We report here that human synovial cells stimulated by interleukin-1 alpha and interleukin-1 beta express mRNA for both IL-8 (neutrophil chemotactic peptide) and monocyte chemotactic protein. IL-1 stimulated synovial cells from both osteoarthritis and rheumatoid arthritis patients exhibited similar mRNA expression of interleukin-8 and monocyte chemotactic protein. A capacity to produce factors selectively chemotactic for neutrophils, lymphocytes and monocytes provides a mechanism whereby synovial cells can facilitate inflammatory arthritis.
We conclude that the amount of soluble particulate contained in the aerosol discharged into the passenger compartment by dual frontal airbag deployment is largely the cause of the observed evoked asthmatic attacks. The alkaline pH of the airbag and carbonate aerosols may have added an additional degree of provocation.
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