Infiltration of neutrophils by intrapleural injection of tumour necrosis factor, interleukin‐1, and interleukin‐8 in rats, and its modification by actinomycin D

Abstract

To assess in vivo chemotactic activity of tumour necrosis factor (TNF), interleukin‐1 (IL‐1), IL‐8, and cytokine‐induced neutrophil chemoattractant (CINC), we injected these cytokines into the pleural cavity of rats. CINC (0.1‐1 μg) and recombinant human IL‐8 (rhIL‐8, 0.2–5 μg) caused neutrophil infiltration into the rat pleural cavity in a dose‐dependent fashion, peaking at 3 h. The number of leukocytes in the peripheral blood did not change significantly. RhTNFα and rhIL‐1α also induced neutrophil accumulation. The dose response curves of rhTNFα (0.67 ng‐6.7 μg) and rhIL‐1α (0.45 ng‐4.5μg) at 3 h were bell shaped. On the other hand, unlike CINC and rhIL‐8, rhTNFα and rhIL‐1α caused transient marked leukopenia at 3 h in a simple dose‐dependent fashion. Concomitant injection of actinomycin D dose‐dependently and completely at 10 μg inhibited neutrophil infiltration induced by rhTNFα (0.67 μg) and rhIL‐1α (0.45 μg) at 3 h. However, that induced by CINC or rhIL‐8 was not affected by actinomycin D. Peaking at 1 h, CINC production in the pleural cavity was found after intrapleural injection of rhTNFα (0.67 μg) or rhIL‐1α (0.45 μg), but not after that of rhIL‐8 (5 μg). The CINC production induced by rhTNFα or rhIL‐1α and the neutrophil infiltration was suppressed by concomitant injection of actinomycin D (1 and 10 μg). These results indicate that CINC and IL‐8 themselves are direct chemoattractants for neutrophils, whereas TNF and IL‐1 induce neutrophil infiltration indirectly via newly synthesized mRNA for chemotactic protein including CINC, which may be involved in neutrophil emigration at local inflammatory sites in rats.

Role of Neutrophil Elastase in Endotoxin-Induced Mucus Hypersecretion in Rat Nasal Epithelium

“…In the present study, intranasal instillation of human recombinant IL-8, which is a strong chemoattractant for rat neutrophils, 22 the 5 rats examined. The fact that epithelial mucus production was observed only in neutrophil-infiltrating epithelia suggests that neutrophils themselves stimulate epithelial mucus production.…”

Proteolysis-inducing factor core peptide mediates dermcidin-induced proliferation of hepatic cells through multiple signalling networks

“…Experiments using the synthetic PIF-core peptide support this conclusion in that proliferation of a similar magnitude was observed. The bell-shaped dose-response curve following Huh7 treatment with synthetic PIF-CP is characteristic of biological responses to several cytokines and growth factors including IFN-γ, IL-6, IL-8 and TNF-α (30)(31)(32)(33). It has also been suggested that bell-shaped dose-response curves may result from the action of an agonist on two separate receptors (34).…”

Transforming growth factor- induces collagen synthesis without inducing IL-8 production in mesothelial cells

“…The IL-8 concentration also correlates with the neutrophil counts in human pleural effusions [26]. Direct intrapleural injection of IL-8 caused neutrophil infiltration into the pleural cavity in rats in a dose-dependent manner [6]. Conversely, addition of IL-8 antibodies neutralised neutrophil chemotaxis [27,28].…”

“…Intrapleural injection of talc stimulates a rapid increase in IL-8 in the pleural cavity and an associated influx of polymorphonuclear cells in both human and animal studies [4][5][6]. Pain and fever, which commonly complicate pleurodesis, are believed to result from the pleural inflammation.…”