Kinetics of mucosal granulocyte activation after gluten challenge in coeliac disease.
OBJECTIVE
To elucidate the dynamics of the rectal inflammatory response to rectal gluten challenge in coeliac disease by measuring inflammatory mediators released by activated neutrophils, eosinophils and mast cells/basophils.


METHODS
The release of myeloperoxidase (MPO), eosinophilic cationic protein (ECP) and histamine was measured continuously during the early challenge period (3-6 h after gluten challenge) in coeliac patients (n = 9) and healthy controls (n = 5). A segmental perfusion technique was used to carry out this part of the study. Another method, the mucosal patch technique, was used to enable studies of the late challenge period (5-48 h after gluten challenge) in coeliac patients (n = 10) and healthy controls (n = 15).


RESULTS
During the early challenge period the MPO levels began to increase as early as 3 h after challenge and increased progressively (p < 0.001) during the next 3 h. A decline in MPO levels was seen 15 h after challenge and another phase of increasing levels at 24 h. The MPO values declined 48 h after challenge but still remained significantly increased (p < 0.05). The ECP levels started to increase 4 h after challenge and increased progressively during the next 2 h (p < 0.05). The ECP kinetics during the late challenge period was similar as for MPO but the relative increase in ECP was more modest. No increase in histamine was found except in one patient who had a transient, early increase of histamine (3-5 h after challenge). No signs of inflammatory reaction to gluten were seen in the controls.


CONCLUSIONS
There is a pronounced neutrophil activation in coeliac patients after rectal gluten challenge. This activation is apparent 4 h after challenge and remains for at least 48 h. A more modest eosinophil activation defined by ECP levels starts 1-2 h later and also remains for at least 48 h. The biphasic pattern of MPO and ECP after challenge suggests a biphasic inflammatory reaction.
Kristjansson
Gudjon
G
Department of Gastroenterology, Hospital General Vall d'Hebron, Barcelona, Spain. gudjon.kristjansson@medsci.uu.se
Serra
Jordi
J
Lööf
Lars
L
Venge
Per
P
Hällgren
Roger
R
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002446:Celiac Disease / Q000175:diagnosis*; D047091:Eosinophil Granule Proteins / Q000032:analysis / Q000378:metabolism*; D005260:Female; D005983:Glutens / Q000493:pharmacokinetics*; D006098:Granulocytes / Q000187:drug effects*; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D018375:Neutrophil Activation; D011336:Probability; D011379:Prognosis; D012016:Reference Values; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
D047091:Eosinophil Granule Proteins; D018836:Inflammation Mediators; D005983:Glutens