Rebound eosinophilia after treatment of hypereosinophilic syndrome and eosinophilic gastroenteritis with monoclonal anti-IL-5 antibody SCH55700.
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.
Kim
Yae-Jean
YJ
NIAID, NIH, Bethesda, MD 20892, USA.
Prussin
Calman
C
Martin
Brian
B
Law
Melissa A
MA
Haverty
Thomas P
TP
Nutman
Thomas B
TB
Klion
Amy D
AD
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002470:Cell Survival; D016207:Cytokines / Q000097:blood; D004802:Eosinophilia / Q000209:etiology*; D004804:Eosinophils / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D005759:Gastroenteritis / Q000628:therapy*; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000628:therapy*; D015848:Interleukin-5 / Q000037:antagonists & inhibitors* / Q000097:blood; D008297:Male; D008875:Middle Aged
D000911:Antibodies, Monoclonal; D016207:Cytokines; D015848:Interleukin-5