Effect of interleukin-16-blocking peptide on parameters of allergic asthma in a murine model.
In this study, we examined whether peptides based on the hydrophilic Cluster of Differentiation (CD) 4-binding part of the amino acid sequence of human interleukin-16 can block interleukin-16-induced chemotaxis of murine lymphocytes in vitro. Peptide 3 was capable of inhibiting interleukin-16-induced chemotaxis of murine splenocytes in vitro. Next, we compared the effects of intra-airway administration of peptide 3 with those of antibodies to interleukin-16 on antigen-induced features in a murine model of allergic asthma. Intra-airway administration of peptide 3 largely inhibited the development of antigen-induced airway hyperresponsiveness while airway eosinophilia was not affected. Similar effects were observed after intranasal application of antibodies to interleukin-16. These results indicate that treatment with peptide 3 causes the same effects as do antibodies to interleukin-16, possibly via the inhibition of interaction between interleukin-16 and its receptor CD4. Therefore, peptide 3 could be useful as a lead compound in attempting to limit airway hyperresponsiveness via binding to CD4.
de Bie
J J
JJ
Department of Pharmacology and Pathophysiology, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, P.O.Box 80.082, 3508 TB, Utrecht, Netherlands.
Henricks
P A
PA
Cruikshank
W W
WW
Hofman
G
G
Nijkamp
F P
FP
van Oosterhout
A J
AJ
D000281:Administration, Intranasal; D000403:Airway Resistance / Q000187:drug effects; D000595:Amino Acid Sequence; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D019138:Antibodies, Blocking / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002469:Cell Separation; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D019410:Interleukin-16 / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D018721:Muscarinic Agonists / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*
D018927:Anti-Asthmatic Agents; D019138:Antibodies, Blocking; D019410:Interleukin-16; D018721:Muscarinic Agonists; D009842:Oligopeptides; D010446:Peptide Fragments; C403321:interleukin-16 (616-631); D016210:Methacholine Chloride; D010047:Ovalbumin