Rebound eosinophilia after treatment of hypereosinophilic syndrome and eosinophilic gastroenteritis with monoclonal anti-IL-5 antibody SCH55700.

Abstract

BACKGROUND:

Hypereosinophilic syndrome and eosinophilic gastroenteritis with peripheral eosinophilia are characterized by sustained eosinophilia and eosinophil-mediated tissue damage. Although treatment with the humanized monoclonal anti-IL-5 antibody SCH55700 resulted in improvement of eosinophilia and clinical symptoms in 6 of 8 of patients with hypereosinophilic syndrome or eosinophilic gastroenteritis with peripheral eosinophilia for as long as 12 weeks, eosinophil counts subsequently rose above baseline levels, accompanied by an exacerbation of symptoms.

OBJECTIVE:

To identify the mechanism underlying this rebound eosinophilia.

METHODS:

Purified eosinophils from patients or normal donors were cultured with IL-5, patient serum, and/or anticytokine antibodies, and eosinophil survival was assessed by flow cytometry. Serum and intracellular cytokine levels were measured by multiplex sandwich ELISA and flow cytometry, respectively.

RESULTS:

Before treatment with SCH55700, in vitro eosinophil survival in media and in response to recombinant IL-5 was similar in patients and normal donors. At 1 month posttreatment, the eosinophil survival curves were unchanged in 4 of 5 patients in media and in all 5 patients in response to recombinant IL-5. Normal eosinophil survival was prolonged in cultures containing posttreatment but not pretreatment sera (pretreatment vs posttreatment, 10.74% vs 73.02% live cells; P = .01). This posttreatment serum effect on eosinophil survival was reversed by the addition of the monoclonal anti-IL-5 antibody TRFK5. Although increased levels of serum IL-5 were observed at 1 month compared with 2 to 3 days posttreatment in 5 of 6 patients ( P = .04), intracellular cytokine analysis did not reveal increased production of IL-5 by peripheral blood mononuclear cells.

CONCLUSIONS:

The rebound eosinophilia after SCH55700 treatment is a result of a serum factor that enhances eosinophil survival. Reversal of this effect by the addition of antibody to IL-5 suggests that this factor may be IL-5 itself.

• Authors: Yae-Jean Kim, Calman Prussin, Brian Martin, Melissa A Law, Thomas P Haverty, Thomas B Nutman, Amy D Klion
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 114 Issue 6 Pg. 1449-55 (Dec 2004) ISSN: 0091-6749 [Print] United States
• PMID: 15577851 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Monoclonal
• Cytokines
• Interleukin-5

Topics

• Adult
• Antibodies, Monoclonal (therapeutic use)
• Cell Survival
• Cytokines (blood)
• Eosinophilia (etiology)
• Eosinophils (physiology)
• Female
• Flow Cytometry
• Gastroenteritis (therapy)
• Humans
• Hypereosinophilic Syndrome (therapy)
• Interleukin-5 (antagonists & inhibitors, blood)
• Male
• Middle Aged