Peptide inhibitor of interleukin-8 (IL-8) reduces staphylococcal enterotoxin-A (SEA) induced neutrophil trafficking to the lung.
Staphylococcal enterotoxin A (SEA) is a superantigen, produced by some strains of Staphylococcus aureus (S. aureus), which can cause a variety of clinical manifestations ranging from food poisoning to shock. SEA can also stimulate human alveolar macrophages to produce interleukin-8 (IL-8), a member of the alpha-chemokine subfamily that activates and is chemotactic for neutrophils. In these studies we showed that in rabbits, intravenous SEA significantly decreased the circulating white blood cell population from a baseline value of 6409 +/- 2027 x 10(3) cells/ml to 1943 +/- 862 x 10(3) cells/ml in 7 h. There was a concommitent increase in IL-8 in the circulating plasma (baseline: 60 +/- 34 pg/ml, 7 h post SEA: 109 +/- 64 pg/ml). The increase in circulating IL-8 was accompanied by a much greater increase in the IL-8 concentration of the epithelial lining fluid (ELF) where the IL-8 increased from 0.05 +/- 0.08 ng/ml (control) to 13.8 +/- 9.3 ng/ml (SEA treated). The increase in IL-8 concentration in the alveolar spaces was paralleled by an increase in both the percentage of neutrophils (1.4 +/- 0.9% (control) to 26.0 +/- 10.8% (SEA treated)) and total number of neutrophils (0.04 +/- 0.02 x 10(6)/ml (control) to 4.8 +/- 3.3 10(6)/ml (SEA treated) in the airspaces, and the numbers of neutrophils in the ELF correlated with the IL-8 concentration r = 0.62, p = 0.006). When antileukinate, a hexapeptide which inhibits the binding of IL-8 to neutrophils, was administered to animals receiving SEA, the IL-8 concentration in the ELF (14.8 +/- 10.7 ng/ml) was not significantly different from the concentration of IL-8 in those animals receiving SEA alone). However, both the percentage of neutrophils (9.5 +/- 3.2%), and the total number of neutrophils (1.3 +/- 1.0 x 10(6)/ml) in the ELF following SEA and antileukinate administration was significantly lower than in animals which only received SEA (p < 0.05). The findings suggest that SEA released into the circulation during a Staphylococcal infection can cause an inflammatory reaction in the lung. Since this reaction is at least partially mediated by IL-8, antileukinate may have pharmacologic potential in reducing the inflammatory reaction.
Miller
E J
EJ
Department of Biochemistry, University of Texas Health Center, Tyler 75710-2003, USA.
Cohen
A B
AB
Peterson
B T
BT
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004768:Enterotoxins / Q000494:pharmacology*; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D016209:Interleukin-8 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007958:Leukocyte Count; D008168:Lung / Q000166:cytology* / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects*; D011817:Rabbits
D004768:Enterotoxins; D016209:Interleukin-8; C026066:enterotoxin A, Staphylococcal