Interleukin-5, eosinophils, and disease

Abstract

OSINOPHIL production can be induced in vitro by E interleukin-3 (IL-3), granulocyte-macrophage colonystimulating factor (GM-CSF), and IL-5.Both IL-3 and GM-CSF have activities on other hemopoietic lineages, whereas IL-5 is specific for the eosinophil/basophil lineage.The activity of IL-5 on basophils has been reviewed recently' and will not be discussed here.There is now good evidence that IL-5 is the major, and possibly the only, cytokine involved in the production of specific eosinophilia.Classically eosinophilia is observed in a restricted number of diseases, most notably helminth infections and allergic diseases.However, although the increase in eosinophil numbers is less spectacular, there is increasing evidence for an involvement of eosinophils in a wider spectrum of diseases.A study of experimental infection of volunteers by the hookworm Necator americanus gave clear evidence for an increase in eosinophils with no significant increase in other blood leucocytes,2 and infection of mice with the cestode Mesocestoides Corti causes a massive increase in blood and peritoneal eosinophils with little effect on the number of ne~trophils.~This biologic specificity, the relatively restricted disease profile of eosinophilia, and the requirement for a functional T-lymphocyte ~y s t e m ~-~ suggested that the control of eosinophilia must be part of the immune response and based on a subset of T celk7Eosinophils are cytotoxic cells capable of killing helminths, parasitic protozoa, chicken erythrocytes, and tumor cells in vitro.For more general reviews and background see Spry,8 Dexter et a1,9 Thompson,'O and Smith and Cook.llTime-lapse cinematography has shown that eosinophils phagocytose and regurgitate red blood cells very rapidly.This is in contrast to neutrophils and macrophages that retain them until they have been broken down.12This explains why eosinophils appear to be less active in comparison to neutrophils in classical phagocytosis assays using yeast or bacteria.They do not retain the particles.It is unclear what this implies for the killing ability of the eosinophil, but it is possible that they are better adapted to attach to large parasites13 rather than to phagocytose small particles. IL-5 STRUCTUREIL-5 is unusual among the T-cell-produced cytokines in being a disulphide-linked homodimeric glycoprotein.It is highly homologous between species, as indicated by the high sequence homology between mouse and human 1L-5 and the cross-reactivity of the protein across a variety of mammalian species.Mature human IL-5 monomer comprises 115 amino acids (molecular weight [M,] of 12,000 and 24,000 for the dimer).The secreted material has an M, of 40,000 to 45,000, and thus nearly half the native material consists of carbohydrate, although this carbohydrate does not appear to be necessary for biologic activity in vitro.14Studies with mouse IL-5 indicate that the monomer has no biologic activity and has no inhibitory activity, suggesting that they do not form high-affinity interactions with the IL-5 receptor (IL-5R).IS The dimer exists in an antiparallel (head to tail) c o n f i g u r a t i ~n .~~-~~