IL-5: biology and potential therapeutic applications.
IL-5 is the predominant cytokine associated with antigen-induced eosinophilic inflammation in the lung. The activation of Th-2 cells leads to the production of IL-5. The pro-eosinophilic effects of IL-5 include: (1) enhanced replication and differentiation of eosinophilic myelocytes; (2) enhanced degranulation of eosinophils; (3) prolonged survival time of eosinophils: and (4) enhanced adhesion of eosinophils. The effects of IL-5 are mediated via the interaction of IL-5 with receptors (IL-5R) that are expressed on the eosinophil cell membrane. Intracellular signalling produced by occupation of the IL-5R by IL-5 occurs via the JAK-STAT system. IL-5 is a 45 kDa glycoprotein consisting of two identical polypeptide chains. The 5'-promoter region of the IL-5 gene contains elements that are down-regulated by glucocorticoids. Anti-IL-5 reagents have the potential to suppress IL-5 activity without the side effects of glucocorticoids. Studies using monoclonal antibodies (mAbs) against IL-5 have established the feasibility of suppressing eosinophilic inflammation by specifically blocking IL-5 activity. Studies with antisense IL-5 are beginning to provide the basis for non-glucocorticoid, sequence-specific oligonucleotide inhibitors of IL-5. Research has begun on the development of mAbs and antisense oligonucleotide inhibitors of IL-5 that can be inhaled and applied topically.
Weltman
J K
JK
Department of Medicine, Brown University School of Medicine, Providence, RI 02912, USA. joel.weltman@brown.edu
Karim
A S
AS
D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5; D004804:Eosinophils / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology* / Q000517:prevention & control; D015848:Interleukin-5 / Q000235:genetics / Q000502:physiology* / Q000627:therapeutic use*; D018418:Th2 Cells / Q000276:immunology
D015848:Interleukin-5