Hematopoietic, immunomodulatory and epithelial effects of interleukin-11

ABSTRACT Interleukin 11 (IL-11) is a pleiotropic cytokine with biological activities on many different cell types. Recombinant human IL-11 (rhIL-11) is produced by recombinant DNA technology

in _Escherichia coli_. Both _in vitro_ and _in vivo_, rhIL-11 has shown effects on multiple hematopoietic cell types. Its predominant _in vivo_ hematopoietic activity is the stimulation of

peripheral platelet counts in both normal and myelosuppressed animals. This activity is mediated through effects on both early and late progenitor cells to stimulate megakaryocyte

differentiation and maturation. rhIL-11 has been approved for the treatment of chemotherapy-induced thrombocytopenia. The hematopoietic effects of rhIL-11 are most likely direct effects on

progenitor cells and megakaryocytes in combination with other cytokines or growth factors. rhIL-11 also induces secretion of acute phase proteins (ferritin, haptoglobin, C-reactive protein,

and fibrinogen) from the liver. The induction of heme oxidase and inhibition of several P450 oxidases have been reported from _in vitro_ studies. _In vivo_, rhIL-11 treatment decreases

sodium excretion by the kidney by an unknown mechanism and induces hemodilution. rhIL-11 also exhibits anti-inflammatory effects in a variety of animal models of acute and chronic

inflammation, including inflammatory bowel disease, inflammatory skin disease, autoimmune joint disease, and various infection-endotoxemia syndromes. rhIL-11 has trophic effects on

non-transformed intestinal epithelium under conditions of mucosal damage. The mechanism of the anti-inflammatory activity of rhIL-11 has been extensively studied. rhIL-11 directly affects

macrophage and T cell effector function. rhIL-11 inhibits tumor necrosis factor-alpha (TNFα), interleukin 1β (IL-1β), interleukin 12 (IL-12), interleukin 6 (IL-6), and nitric oxide (NO)

production from activated macrophages _in vitro_. The inhibition of cytokine production was associated with inhibition of nuclear translocation of the transcription factor, nuclear factor

kappa B (NF-κB). The block to NF-κB nuclear translocation correlates with the ability of rhIL-11 to maintain or enhance production of the inhibitors of NF-κB, IκB-α and IκB-β. In addition to

effects on macrophages, rhIL-11 also reduces CD4+ T cell production of Th1 cytokines, such as IFNγ induced by IL-12, while enhancing Th2 cytokine production. rhIL-11 also blocks IFNγ

production _in vivo_. The molecular effects of rhIL-11 have also been studied in a clinical trial. Molecular analysis of skin biopsies of patients with psoriasis before and during rhIL-11

treatment demonstrates a decrease in mRNA levels of TNFα, IFNγ and iNOS. These activities suggest that in addition to its thrombopoietic clinical use, rhIL-11 may also be valuable in the

treatment of inflammatory diseases. The clinical utility of the anti-inflammatory properties of rhIL-11 is being investigated in patients with Crohn’s disease, psoriasis and rheumatoid

arthritis. These diseases are believed to be initiated and maintained by activated CD4+ Th1 cells in conjunction with activated macrophages. Access through your institution Buy or subscribe

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AND AFFILIATIONS * Genetics Institute, Cambridge and Andover, MA 02140/01810, USA US Schwertschlag, WL Trepicchio, KH Dykstra, JC Keith, KJ Turner & AJ Dorner Authors * US Schwertschlag

View author publications You can also search for this author inPubMed Google Scholar * WL Trepicchio View author publications You can also search for this author inPubMed Google Scholar * KH

Dykstra View author publications You can also search for this author inPubMed Google Scholar * JC Keith View author publications You can also search for this author inPubMed Google Scholar

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Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Schwertschlag, U., Trepicchio, W., Dykstra, K. _et al._ Hematopoietic, immunomodulatory and

epithelial effects of interleukin-11. _Leukemia_ 13, 1307–1315 (1999). https://doi.org/10.1038/sj.leu.2401514 Download citation * Received: 06 April 1999 * Accepted: 31 May 1999 * Published:

09 September 1999 * Issue Date: 01 September 1999 * DOI: https://doi.org/10.1038/sj.leu.2401514 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this

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KEYWORDS * rhIL-11