New means to monitor the effect of glucocorticoid therapy in children.
OBJECTIVE
To study the individual effects of glucocorticoid (GC) therapy on the state of immune activation in patient serum.


METHODS
We developed a novel assay in which the effect of corticosteroid-treated patient serum on healthy donor peripheral blood mononuclear cells (target cells) was studied, with a panel of markers for effector [interferon (IFN)gamma and interleukin (IL)-5] and regulatory T cells (FOXP3 and glucocorticoid-induced tumor necrosis factor receptor, GITR). The study group comprised 19 children with inflammatory bowel disease. The individual effect of patient serum on target cells was analyzed prior to GC therapy and 2 wk later.


RESULTS
The effect of GC therapy mediated by patient serum was seen as a decrease in the target cells expression of regulatory T-cell-related markers GITR (median suppression 24%, range of suppression 1%-63%, in 2 cases increase of 6% and 77%, P < 0.01 for mitogen-activated target cells) and FOXP3 (median suppression 33%, range of suppression 0%-79%, in one case an increase of 173%, P < 0.05 for resting cells), and secretion of IFNgamma [from a mean of 87 700 pg/mL (SD 33 900 pg/mL) to 60 900 pg/mL (SD 44 200 pg/mL) in mitogen-activated target cells, 13 of the cases showed a decrease, P < 0.01]. The total or weight-related prednisolone dose did not correlate with the patient-serum-induced changes in the target cell markers.


CONCLUSIONS
GC response could be monitored at an individual level by studying the effect of patient serum on signaling pathways of target immune cells.
Rintamäki
Hanne
H
Division of Gastroenterology, Hospital for Children and Adolescents, University of Helsinki, Box 281, Helsinki, FIN-00029, Finland.
Salo
Harri M
HM
Vaarala
Outi
O
Kolho
Kaija-Leena
KL
D000293:Adolescent; D000328:Adult; D001681:Biological Assay; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D053450:Glucocorticoid-Induced TNFR-Related Protein; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D015848:Interleukin-5 / Q000235:genetics / Q000378:metabolism; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D011237:Predictive Value of Tests; D011239:Prednisolone / Q000627:therapeutic use*; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013997:Time Factors; D016896:Treatment Outcome
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D005765:Gastrointestinal Agents; D053450:Glucocorticoid-Induced TNFR-Related Protein; D005938:Glucocorticoids; C508599:IL5 protein, human; D015848:Interleukin-5; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C491405:TNFRSF18 protein, human; D007371:Interferon-gamma; D002097:C-Reactive Protein; D011239:Prednisolone