A synthetic VIP peptide analogue inhibits neutrophil recruitment in rat airways in vivo.
Currently, there is no effective pharmacotherapy against exaggerated mobilisation of neutrophils in human airway diseases such as chronic obstructive pulmonary disease and asthma. We evaluated the effect of two synthetic vasoactive intestinal peptide (VIP)-like analogues on cytokine-induced neutrophil recruitment in airways in vivo. Recombinant interleukin (IL)-1 beta was administered intratracheally (i.t.) to intubated, spontaneously breathing Sprague-Dawley rats. The rats were pretreated either with a VIP synthetic peptide analogue, a pituitary adenylate cyclase-activating peptide (PACAP)-1-27 synthetic analogue, the beta(2)-adrenoceptor agonist salbutamol or vehicle, systemically or locally. Differential cell counts were performed on bronchoalveolar lavage fluid (BALf) cytospins. Effects on mean arterial blood pressure (MAP) were monitored in separate experiments. Systemic administration of the VIP analogue, the PACAP analogue and salbutamol attenuated the cytokine-induced increase in BALf neutrophil number. Local administration of the VIP analogue and salbutamol, but not the PACAP analogue, also decreased the neutrophil number in BALf. Local administration of the VIP analogue and salbutamol caused a transient decrease in MAP. Systemic or local administration of a synthetic VIP peptide analogue inhibits cytokine-induced neutrophil recruitment in airways in vivo. This action is exerted without severe, sustained cardiovascular side effects, and deserves to be further evaluated in obstructive pulmonary diseases in human.
Sergejeva
Svetlana
S
Lung Pharmacology Group, Department of Respiratory Medicine and Allergology, Göteborg University, Guldhedsgatan 10A, SE 41346 Gothenburg, Sweden. Svetlana.Sergejeva@lungall.gu.se
Hoshino
Hiroshi
H
Yoshihara
Shigemi
S
Kashimoto
Kazuhiza
K
Lötvall
Jan
J
Lindén
Anders
A
D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects*; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology; D020556:Neutrophil Infiltration / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017207:Rats, Sprague-Dawley; D014660:Vasoactive Intestinal Peptide / Q000138:chemical synthesis / Q000494:pharmacology*
C495401:ADCYAP1 protein, human; C495403:Adcyap1 protein, rat; D016207:Cytokines; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014660:Vasoactive Intestinal Peptide; D000420:Albuterol