Cooperation between interleukin-5 and the chemokine eotaxin to induce eosinophil accumulation in vivo.
Experiments were designed to study the effect of systemically administered IL-5 on local eosinophil accumulation induced by the intradermal injection of the chemokine eotaxin in the guinea pig. Intravenous interleukin-5 (IL-5) stimulated a rapid and dramatic increase in the numbers of accumulating eosinophils induced by i.d.-injected eotaxin and, for comparison, leukotriene B4. The numbers of locally accumulating eosinophils correlated directly with a rapid increase in circulating eosinophils: circulating eosinophil numbers were 13-fold higher 1 h after intravenous IL-5 (18.3 pmol/kg). This increase in circulating cells corresponded with a reduction in the number of displaceable eosinophils recovered after flushing out the femur bone marrow cavity. Intradermal IL-5, at the doses tested, did not induce significant eosinophil accumulation. We propose that these experiments simulate important early features of the tissue response to local allergen exposure in a sensitized individual, with eosinophil chemoattractant chemokines having an important local role in eosinophil recruitment from blood microvessels, and IL-5 facilitating this process by acting remotely as a hormone to stimulate the release into the circulation of a rapidly mobilizable pool of bone marrow eosinophils. This action of IL-5 would be complementary to the other established activities of IL-5 that operate over a longer time course.
Collins
P D
PD
Department of Applied Pharmacology, National Heart and Lung Institute, London, United Kingdom.
Marleau
S
S
Griffiths-Johnson
D A
DA
Jose
P J
PJ
Williams
T J
TJ
D000818:Animals; D001853:Bone Marrow / Q000502:physiology; D001854:Bone Marrow Cells; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D047209:Eosinophil Peroxidase; D004802:Eosinophilia / Q000097:blood; D004804:Eosinophils / Q000502:physiology*; D006168:Guinea Pigs; D007271:Injections, Intradermal; D007275:Injections, Intravenous; D015848:Interleukin-5 / Q000008:administration & dosage / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000494:pharmacology; D008297:Male; D010544:Peroxidases / Q000032:analysis; D012867:Skin / Q000737:chemistry / Q000187:drug effects*
D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D015848:Interleukin-5; D007975:Leukotriene B4; D047209:Eosinophil Peroxidase; D010544:Peroxidases